Edit Target: (Will delete Record if Target field = "Delete")

tid	Target	inCan	Name	Source	Type	Desc
1312-	0-reuse	?	0-reuse
1126-	12LOX	↑	12‐lipoxygenase			<b>12‐lipoxygenase</b> (commonly abbreviated as 12-LOX) <br> 12-LOX (12-lipoxygenase) is an enzyme that plays a role in the metabolism of polyunsaturated fatty acids—in particular, converting arachidonic acid into bioactive lipid mediators such as 12-hydroxyeicosatetraenoic acid (12-HETE). <br> -12-LOX is implicated in several mechanisms that can promote cancer, including supporting inflammation, cell survival, angiogenesis, and metastasis.<br> High 12-LOX expression in several cancer types is generally correlated with more aggressive disease and poorer clinical outcomes. However, the prognostic significance may vary between cancers and patient populations. Ongoing research is aiming to clarify:<br> – Whether 12-LOX can be reliably used as a prognostic biomarker<br> – And whether targeting 12-LOX might serve as a therapeutic strategy in cancer management.<br> – Increased Levels of 12-LOX in ESCC Patients with Poor Prognosis<br>
684-	14-3-3 proteins	↑	14-3-3 proteins			<b>14-3-3 proteins</b> are a family of conserved regulatory molecules that play a crucial role in various cellular processes, including cell cycle regulation, apoptosis, and signal transduction. 14-3-3 proteins bind to a wide range of proteins, including kinases, phosphatases, and transcription factors, and modulate their activity, localization, and stability.<br> 14-3-3 proteins can bind to and inhibit pro-apoptotic proteins, such as BAD and BAX, and promote cell cycle progression by binding to and activating cyclin-dependent kinases.<br> Overexpression: breast, lung, ovarian, pancreatic<br> Altered: colon, prostate, liver brain<br>
1262-	4-HNE	↑	4‑Hydroxynonenal			<b>4‑Hydroxynonenal (4‑HNE)</b> is a key bioactive aldehyde generated during lipid peroxidation, and it can form adducts with proteins, DNA, and other biomolecules.<br> <br> 4‑HNE can act as a “double‐edged sword”. At moderate concentrations, it might activate signaling pathways that promote cell proliferation and survival, potentially contributing to tumor growth. At higher concentrations, the same molecule may induce cytotoxicity and apoptosis. <br> <br> -A biomarker of ferroptosis(high levels)<br> -Elevated levels of 4‑HNE adducts are sometimes associated with chemoresistance and poor clinical outcomes, highlighting its potential role in prognostication.<br>
736-	4E-BP1	↓	eukaryotic translation initiation factor 4E-binding protein 1		protein	<b>4E-BP1</b> (eukaryotic translation initiation factor 4E-binding protein 1) is a protein that plays a crucial role in regulating cell growth, proliferation, and survival. It is a key downstream target of the mTOR (mechanistic target of rapamycin) signaling pathway, which is often dysregulated in cancer.<br> Phosphorylated and inactivated in: breast, lung, CRC, prostate, GBM, pancreatic, ovarian, melanoma, HCC.<br> The level of phosphorylation can impact the prognosis and treatment response.<br>
1119-	5HT	↑	5-hydroxytryptamine			<b>Serotonin (5-hydroxytryptamine or 5-HT)</b> is best known as a neurotransmitter; however, it also plays diverse roles in peripheral tissues, including modulation of cell proliferation, angiogenesis, and immune responses. <br> <br> Several studies have identified the expression of multiple 5-HT receptors (e.g., 5-HT1A, 5-HT2A, and 5-HT7) in breast cancer cells.<br> Serotonin may promote tumor cell proliferation and can influence breast cancer progression through receptor-mediated signaling pathways.<br> <br> Expression of 5-HT and its receptors is documented in various cancers including breast, colorectal, pancreatic, prostate, and hepatocellular carcinoma.<br> Overexpression of particular 5-HT receptors often correlates with increased cell proliferation, angiogenesis, and metastatic potential.<br> High levels of 5-HT receptor expression generally serve as a marker for poor prognosis, although the exact prognostic implications vary depending on the specific receptor subtype and tumor type.<br> <br> -Vomiting caused by chemotherapy was thought to result from the fact that the chemotherapeutics stimulated the secretion of 5-HT in intestinal chromaffin cells, and then 5-HT acted on 5-HT receptor which caused excitation of nerves and vomiting reflex.<br>
1090-	5LO	↑	5-lipoxygenase (5-LO)			<b>5‑Lipoxygenase (5‑LO)</b> is an enzyme that catalyzes the oxygenation of arachidonic acid to produce leukotrienes and other bioactive lipid mediators. It is a member of the lipoxygenase family and plays a key role in inflammatory responses.<br> <br> 5‑LO is overexpressed in various malignancies, particularly those with a strong inflammatory component.<br> Overexpression of 5‑LO is often detected in tumor cells as well as in stromal cells (e.g., tumor-associated macrophages) within the tumor microenvironment.<br> Elevated 5‑LO expression is frequently linked with increased tumor proliferation, enhanced angiogenesis, and higher metastatic potential—factors that often correlate with a poor prognosis.<br>
834-	67LR	↑	67-kDa laminin receptor			<b>67LR</b> (67-kDa laminin receptor) is a protein that plays a role in cell adhesion, migration, and signaling.<br> 67LR is often overexpressed and has been associated with:<br> - Increased cell migration and invasion<br> - Enhanced tumor growth and metastasis<br> - Resistance to chemotherapy and radiation therapy<br>
1217-	6PGD	↑	6-phosphogluconate dehydrogenase			<b>6PGD</b> is a key enzyme in the oxidative branch of the pentose phosphate pathway (PPP), contributing to nucleotide biosynthesis and the production of NADPH. This activity is essential for maintaining redox homeostasis and supporting anabolic processes in rapidly proliferating cells.<br> <br> -In several cancers, elevated 6PGD expression or activity is associated with aggressive tumor behavior and poorer prognosis.<br>
621-	ABC	↑	ABC transporter			<b>ABC (ATP-binding cassette)</b> transporters are a family of proteins that play a crucial role in the transport of various molecules across cell membranes.<br> ABC transporters have been implicated in the development of multidrug resistance, which is a major obstacle in cancer treatment.<br> Overexpression of certain ABC transporters, such as P-glycoprotein (P-gp), has been observed in various types of cancer, including breast, lung, and colon cancer.<br> Examples of ABC transporters implicated in cancer include:<br> - P-glycoprotein (P-gp, ABCB1)<br> - Multidrug resistance-associated protein 1 (MRP1, ABCC1)<br> - Breast cancer resistance protein (BCRP, ABCG2)<br> Prognostic Implications<br> -Drug Resistance: High expression of ABC transporters is often linked to resistance against chemotherapy, leading to treatment failure and poor patient outcomes.<br> -Survival Rates: Patients with tumors expressing high levels of certain ABC transporters may have lower overall survival rates.<br> Target for Therapy: Inhibitors of ABC transporters are being explored as potential adjuncts to improve the efficacy of chemotherapy.<br>
900-	ABCG2	↑	ATP-binding cassette sub-family G member 2			<b>ATP-binding cassette sub-family G member 2 (ABCG2)</b> is a protein that plays a crucial role in the transport of various substances across cell membranes, including drugs, lipids, and xenobiotics. ABCG2 is often high and associated with poor prognosis.<br>
1-	ABL1	↑	Tyrosine-protein kinase ABL1	CGL-Driver Genes	Oncogene	<b>ABL1</b> is a protein tyrosine kinase involved in cell differentiation, division and stress response.<br> ABL1 (Abelson murine leukemia viral oncogene homolog 1) is a gene that encodes a protein tyrosine kinase, which plays a crucial role in various cellular processes, including cell division, differentiation, and response to stress.<br> ABL1, its role as an oncogene is most prominently illustrated by the BCR-ABL fusion protein, which is formed through a chromosomal translocation between the ABL1 gene and the BCR gene.<br> High ABL1 Expression: In some cancers, high levels of ABL1 expression may correlate with poor prognosis, while in others, it may not have a significant impact.<br>
983-	Ac-histone H3	↓	Acetylated Histone H3			<b>Acetylated histone H3</b> refers to histone H3 proteins that carry acetyl groups, typically on lysine residues, which leads to a more relaxed chromatin structure and generally correlates with active gene transcription.<br> – Levels of Ac-histone H3 can serve as a biomarker reflecting the balance between histone acetyltransferase (HAT) activity and HDAC activity in the cell.<br> <br> • Role in Cancer:<br> – Altered acetylation levels may contribute to dysregulated gene expression in cancer cells.<br>   – Low levels of histone acetylation (including Ac-histone H3) are often associated with the silencing of tumor suppressor genes, whereas increased acetylation after treatment with HDAC inhibitors is correlated with reactivation of key regulatory pathways.<br>   – The acetylation state of histone H3 can be used as an indicator of treatment response, and higher acetylation levels after HDAC inhibition often correlate with favorable treatment outcomes.<br> <br> • Therapeutic and Immunotherapy Implications:<br> – HDAC inhibitors aim to increase acetylated histone levels (including Ac-histone H3), thereby promoting a more open chromatin conformation that facilitates transcription of genes involved in differentiation, apoptosis, and immune recognition.<br> <br> – Increased acetylation can enhance the expression of cancer antigens and immune modulatory molecules, potentially sensitizing tumor cells to immune-mediated attack.<br>   – Combination therapies that include HDAC inhibitors and immunotherapeutic agents (such as checkpoint inhibitors) are being actively investigated to enhance antitumor responses by both directly affecting cancer cell survival pathways and by modulating the tumor microenvironment.<br>
549-	ACAA1	⇅	Acetyl-CoA Acyltransferase 1			<b>ACAA1</b> is a Protein Coding gene. <br> decreased ACAA1 expression is correlated with poor prognosis and decreases immune infiltration of CD4+ T cells in LUAD and LUSC. <br> ACAA1 is highly expressed in the luminal androgen receptor (LAR) subtype of TNBC compared with adjacent normal tissues in our TNBC proteomics dataset. Inhibition of ACAA1 restrained TNBC proliferation and potentiated the response to the cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor abemaciclib.<br> The prognostic value of ACAA1 in cancer can vary:<br> High Expression: In some cancers, high levels of ACAA1 expression have been associated with poor prognosis, possibly due to its role in promoting tumor growth and survival.<br> Low Expression: Conversely, in other contexts, low expression levels may correlate with aggressive tumor behavior and worse outcomes.<br>
932-	ACC	↑	Acetyl-CoA Carboxylase		enzyme	</b>ACC-α (Acetyl-CoA Carboxylase alpha)</b> is a cytosolic isoform of ACC that is primarily involved in the regulation of fatty acid synthesis in lipogenic tissues, such as liver and adipose tissue. ACC-α is a key enzyme in the biosynthesis of fatty acids, particularly in the context of de novo lipogenesis.<br> ACC is a biotin-containing enzyme that exists in two main isoforms: ACC-α and ACC-β.<br> Overexpression of ACC-α has been linked to increased fatty acid synthesis, which can contribute to cancer cell growth and survival.<br> ACC-β (Acetyl-CoA Carboxylase beta) is a mitochondrial isoform of ACC that is primarily involved in the regulation of fatty acid oxidation.<br> In general, high ACC expression is associated with:<br> - Poor prognosis<br> - Increased tumor size<br> - Metastasis<br> - Resistance to chemotherapy<br> -Poor response to treatment<br> Low ACC expression is associated with:<br> - Better prognosis<br> - Smaller tumor size<br> - Less metastasis<br> - Better response to chemotherapy<br> - Better response to treatment<br>
605-	ACC-α	↑	Acetyl-CoA Carboxylase alpha			<b>An enzyme</b> that plays a crucial role in the regulation of fatty acid synthesis. Research has shown that ACC-α is overexpressed in various types of cancer, including breast, lung, and colon cancer.<br>
1033-	ACC1	↑	acetyl‐CoA carboxylase 1			ACC1 (encoded by the ACACA gene) is a key enzyme in de novo lipogenesis. It catalyzes the carboxylation of acetyl‐CoA to malonyl‐CoA, a critical step in fatty acid synthesis. Because lipids are essential for membrane synthesis and energy storage, ACC1 plays a critical role in cell growth and metabolism. ACC1 plays a central role in fatty acid synthesis, and its dysregulation is closely linked to cancer metabolism. In many cancer types, overexpression of ACC1 is associated with: -Enhanced lipid production to support rapid proliferation, -Aggressive tumor behavior and potentially poorer prognosis, -Promotion of a vulnerable metabolic state that could be targeted therapeutically. ACC1’s expression level may serve as a prognostic marker. Studies have suggested that patients with tumors showing high ACC1 expression may have decreased overall survival or may progress more rapidly.
2-	ACLY	↑	ATP citrate lyase			<b>ACLY</b> links energy metabolism provided by catabolic pathways to biosynthesis. ACLY, which has been found to be overexpressed in many cancers, converts citrate into acetyl-CoA and OAA.ATP citrate lyase exhibited upregulation in various tumours.<br> General Tumour Biomarker<br> •ACLY is a key enzyme in cancer metabolism.<br> •ACLY is involved in glucose and lipid metabolism.<br> •Many ACLY inhibitors were developed as anti-cancer agents.<br> <br> ACLY is a key enzyme in cellular metabolism that converts citrate into acetyl‐CoA and oxaloacetate. Acetyl‐CoA is a substrate for lipid synthesis and protein acetylation, processes that are often upregulated in cancer cells to support rapid growth and proliferation.<br> <br> ACLY is found overexpressed in many aggressive cancers. ACLY abundantly consumes citrate from nutrient catabolism (especially glucose and glutamine) to support protein acetylation and intense nucleotide and lipid synthesis. The significant decrease in cytosolic citrate appears to play a central role in cancer metabolism by enhancing the Warburg effect and activating the PI3K / AKT axis promoting ACLY activity in a feedback loop. Thus, the inhibition of factors regulating its expression (such as SREBP1) and its activation (such as AKT) could have an <a href="https://pubmed.ncbi.nlm.nih.gov/31830561/" > anti-proliferative effect. </a> <br> <br> Elevated ACLY expression has been observed in a number of cancers. In many studies, high levels of ACLY have been associated with more aggressive disease and poorer prognoses.<br> <br> Natural ACLY Inhibitors<br> -Hydroxycitrate (HCA):(widely studied)<br> -EGCG<br> -Quercetin<br> -Resveratrol<br> -Luteolin<br> -Citrate<br> -Cucurbitacin B<br> -Emodin?<br>
957-	ACOX1	↑	Acyl-CoA Oxidase 1			<b>ACOX1 (Acyl-CoA Oxidase 1)</b> is an enzyme that plays a crucial role in the regulation of fatty acid metabolism, particularly in the breakdown of fatty acids in peroxisomes.<br> <br> ACOX1 is typically overexpressed and is associated with poor prognosis and reduced overall survival in breast, lung, and colon cancers.<br> -ACOX1 expression is also associated with increased risk of metastasis and recurrence in various types of cancer.<br>
867-	ACSL4	↑	Acyl-CoA Synthetase Long-Chain Family Member 4			<b>ACSL4 (Acyl-CoA Synthetase Long-Chain Family Member 4)</b> is a protein that plays a crucial role in the regulation of fatty acid metabolism, particularly in the context of cancer.<br> ACSL4 has been shown to be highly expressed in various types of cancer.<br>
962-	ACSL5	↑	(Acyl-CoA Synthetase Long Chain Family Member 5			<b>The ACSL5 gene</b> (Acyl-CoA Synthetase Long Chain Family Member 5) is a key regulator of fatty acid metabolism, particularly in the activation of long-chain fatty acids. The ACSL5 gene is overexpressed in various types of cancer.<br> <br> ACSL5 gene is a key regulator of fatty acid metabolism and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.<br>
786-	ACSS2	↑	Acyl-CoA Synthetase Short Chain Family Member 2			<b>ACSS2</b> (Acyl-CoA Synthetase Short Chain Family Member 2) is an enzyme that plays a crucial role in the metabolism of fatty acids.<br> ACSS enzymes (mainly ACSS1 in mitochondria and ACSS2 in the cytosol and nucleus) convert acetate into acetyl‐CoA.<br> ACSS2 is overexpressed in: breast, lung, CRC, prostate, pancreatic, GBM, ovarian, liver, Esophageal cancers.<br> <br> -Upregulation of ACSS2 has been observed in various cancers, where it enables cancer cells to maintain acetyl‐CoA levels for Lipid synthesis needed for membrane biogenesis.<br> <br>
507-	ACTA2	↑	Actin Alpha Cardiac Muscle 2			<b>ACTA2</b> (Actin Alpha Cardiac Muscle 2) is a gene that encodes a protein involved in the structure and function of smooth muscle cells. It plays a crucial role in various physiological processes, iACTA2 has been studied for its role in the tumor microenvironment, particularly in relation to cancer-associated fibroblasts (CAFs) and the extracellular matrix. CAFs, which often express ACTA2, can influence tumor progression, metastasis, and response to therapy. ncluding muscle contraction and the maintenance of vascular tone.<br> High levels of ACTA2 are often correlated with aggressive tumor behavior and poor patient outcomes.<br>
3-	ACVR1B	⇅	activin A receptor, type IB	CGL-Driver Genes	TSG	<b>Diseases</b> associated with ACVR1B include Pancreatic Cancer.<br> Activin A receptor type IB (ACVR1B) is a gene that encodes a signaling protein that functions in growth and differentiation.<br> <br> The prognostic value of ACVR1B expression can vary:<br> High Expression: In some cancers, high levels of ACVR1B may be associated with poor prognosis, indicating aggressive tumor behavior.<br> Low Expression: Conversely, low expression levels may correlate with better outcomes in certain contexts.<br> Tumor Suppressor Role<br> In some contexts, ACVR1B has been suggested to have tumor suppressor-like functions:<br> <br> Inhibition of Proliferation: ACVR1B can mediate growth inhibition in certain cell types, and its activation may lead to apoptosis in response to specific signals.<br> Regulation of Cell Cycle: It may play a role in regulating the cell cycle, which is a critical aspect of tumor suppression<br> Oncogenic Role<br> Conversely, in other contexts, ACVR1B may exhibit oncogenic properties:<br> <br> Tumor Progression: In some cancers, altered expression of ACVR1B can be associated with tumor progression and metastasis.<br> Context-Dependent Effects: The effects of ACVR1B can vary based on the presence of other signaling molecules and the specific tumor microenvironment.<br>
994-	ADAM17	↑	A Disintegrin and Metalloprotease 17			<b>ADAM17</b> (A Disintegrin and Metalloprotease 17), also known as TACE (Tumor Necrosis Factor-α Converting Enzyme), is a membrane-anchored protease.<br> – It is best known for cleaving and releasing the extracellular domains (ectodomains) of various cell surface proteins, a process called “ectodomain shedding.”<br> <br> Numerous studies have documented increased ADAM17 expression in several cancers, such as breast, lung, colon, and pancreatic cancers.<br> – Upregulation often correlates with enhanced release of growth factors (e.g., EGF family ligands) and cytokines that may drive tumor growth and modify the tumor microenvironment.<br> – Higher levels of ADAM17 have been linked with more aggressive tumor characteristics, including increased invasiveness, metastasis, and resistance to certain therapies.<br> – In cancers such as breast and lung, elevated ADAM17 expression is often associated with poor clinical prognosis.<br>
1191-	adiP	↓	adiponectin			<b>Adiponectin</b> is an adipokine with anti-inflammatory and insulin-sensitizing properties, and its effects on tumor biology are thought to be mediated through influences on cell proliferation, apoptosis, and metabolic regulation.<br> <br> Adiponectin is a key metabolic hormone whose levels have been associated with cancer risk and prognosis across multiple tumor types. Generally, lower adiponectin levels tend to correlate with more aggressive tumor phenotypes and poorer outcomes, while higher levels may offer a degree of protection.<br>
1054-	ADP:ATP	↑	ADP/ATP ratio			<b>ADP/ATP ratio</b> is a key indicator of a cell’s energy state and mitochondrial function. In the context of cancer, shifts in the ADP/ATP ratio reflect changes in metabolic activity, mitochondrial efficiency, and overall cellular bioenergetics. <br> The ADP/ATP ratio reflects the balance between energy consumption and production. A high ADP/ATP ratio indicates lower energy reserves (or higher energy consumption), while a low ratio suggests abundant ATP availability.<br> • Mitochondrial Function and Metabolism:<br> – Cancer cells often reprogram their metabolism (the “Warburg effect”) to favor glycolysis even in the presence of oxygen. This metabolic shift can affect the ADP/ATP ratio.<br> – Mitochondrial dysfunction, commonly observed in tumors, may also lead to altered ADP/ATP ratios, impacting how cells respond to metabolic stress.<br> <br> • Elevated ADP/ATP Ratio:<br> – In some aggressive tumors, an elevated ADP/ATP ratio can be a sign of mitochondrial stress or increased energy turnover.<br> – This state may result from rapid proliferation, increased energy demand, or inefficient ATP production.<br> <br> • Reduced ADP/ATP Ratio:<br> – Alternatively, some cancer cells may maintain a lower ADP/ATP ratio by upregulating glycolysis or oxidative phosphorylation, ensuring a steady ATP supply to fuel growth and survival.<br> – Tumors with a robust bioenergetic capacity may display lower ratios, possibly correlating with resistance to energetic stress.<br> <br> An elevated or imbalanced ADP/ATP ratio has been associated with aggressive tumor behavior and may predict poor prognosis in certain contexts, although its exact role can vary by tumor type.<br>
1015-	AEG1	↑	Astrocyte Elevated Gene-1			<b>AEG-1</b> (Astrocyte Elevated Gene-1), also known as Metadherin (MTDH) or LYRIC, is an oncogene that has garnered considerable attention due to its multifaceted roles in tumor progression, metastasis, and chemoresistance. <br> AEG-1 is involved in several cellular processes including proliferation, migration, invasion, angiogenesis, and epithelial-to-mesenchymal transition (EMT).<br> It influences multiple signaling pathways such as PI3K/AKT, NF-κB, and Wnt/β-catenin, which are critical for promoting survival, proliferation, and metastatic potential.<br> AEG-1’s ability to interact with various proteins and pathways makes it a central hub in fostering a supportive environment for tumor growth and progression.<br> <br> AEG-1 is overexpressed in a wide range of cancers including breast, prostate, liver (hepatocellular carcinoma), glioblastoma, melanoma, and colorectal cancers, among others.<br> High expression levels are frequently detected in advanced tumor stages and often correlate with aggressive tumor phenotypes.<br>
829-	AFP	↑	α-fetal protein		biomarker	<b>α-fetal protein (AFP)</b> is a protein that is typically produced by the liver and yolk sac of a developing fetus. In adults, high levels of AFP in the blood can be a sign of certain types of cancer, particularly those of the liver, testes, and ovaries.<br> <br> -AFP is primarily known as a serum biomarker in hepatocellular carcinoma (HCC), but its expression and prognostic significance can also extend to other malignancies. <br>
679-	AGRN	↑	agrin		gene	<b>The AGRN gene</b>, also known as agrin, is a gene that encodes a protein involved in the development and maintenance of the neuromuscular junction. <br> AGRN gene has been found to be overexpressed in several types of tumors, including breast, lung, and colon cancer. The overexpression of AGRN has been associated with tumor progression, metastasis, and poor prognosis.<br>
584-	AhR	↑	aryl hydrocarbon receptor			<b>AhR</b> is a ligand-activated transcription factor that plays a crucial role in regulating various cellular processes, including cell growth, differentiation, and immune responses.<br> AhR is overexpressed in lung cancer cells and is associated with poor prognosis.<br> -Cell proliferation: AhR activation promotes cell growth and proliferation.<br> -Apoptosis: AhR activation inhibits apoptosis (programmed cell death), allowing cancer cells to survive.<br> -Angiogenesis: AhR activation promotes the formation of new blood vessels, which is essential for tumor growth.<br> -Immune suppression: AhR activation inhibits the immune response, allowing cancer cells to evade immune detection.<br> AhR regulates expression of CYP1A1, CYP1B1, and COX-2<br> AhR is often overexpressed in various types of cancer, including breast, lung, liver, and skin cancer. AhR expression is often higher in tumor cells compared to normal cells.<br>
520-	AIF	↑	Apoptosis-Inducing Factor			<b>AIF</b> is a mitochondrial oxidoreductase that contributes to cell death programmes and participates in the assembly of the respiratory chain. <br> Nuclear translocation of AIF occurs during cell death and has been associated with human disorders. Expression Levels:<br> AIF is often found to be overexpressed in several types of cancers, including breast, lung, and colorectal cancers.<br> The expression of AIF can vary significantly between different tumor types and even among patients with the same type of cancer.<br> Survival Rates:<br> High levels of AIF expression have been associated with poor prognosis in certain cancers, indicating a potential role in tumor aggressiveness and metastasis.<br> Conversely, low AIF expression may correlate with better survival outcomes in some contexts.<br> Overexpression: In many cancers, AIF is overexpressed, which is often associated with poor prognosis, increased tumor aggressiveness, and resistance to therapy.<br>
1294-	AIM2	↓	Absent In Melanoma 2			<b>AIM2</b> (Absent In Melanoma 2)<br> -AIM2 is a cytosolic pattern recognition receptor that belongs to the PYHIN (pyrin and HIN domain) family.<br> -It is best known for its role in the innate immune system: upon sensing cytosolic double‐stranded DNA, AIM2 forms an inflammasome complex, leading to the activation of caspase-1, secretion of pro-inflammatory cytokines (such as IL-1β and IL-18), and induction of a form of cell death termed pyroptosis.<br> <br> - AIM2 was initially identified for its reduced expression in melanoma cells compared to normal tissue.<br> Reduced AIM2 expression in melanoma has been associated with impaired inflammasome activation and a loss of a potential tumor-suppressive function.<br> In melanoma, downregulation of AIM2 may correlate with a more aggressive tumor phenotype and poorer prognosis, suggesting a protective role in this context.<br> -In colorectal cancer, studies have noted that AIM2 expression can be lost or diminished in tumor cells.<br> Lower levels of AIM2 have been associated with increased cell proliferation, reduced apoptosis, and enhanced tumor progression.<br>
456-	AKR1C2	↑	Aldo-keto reductase family 1 member C2			<b>Studies</b> have shown that AKR1C2 is involved in regulating tumor invasion, migration, and other malignant phenotypes, eliminating reactive oxygen species (ROS), promoting chemotherapy resistance of tumor cells, and has prognostic value in some cancers.<br> <br> Overall Survival: High expression levels of AKR1C2 have been correlated with poor overall survival in several cancer types, suggesting that it may serve as a negative prognostic marker.<br>
4-	Akt	↑	Protein kinase B	HalifaxProj(inhibit)		<b>Akt1</b> is involved in cellular survival pathways, by inhibiting apoptotic processes; Akt2 is an important signaling molecule in the insulin signaling pathway. It is required to induce glucose transport.<br> <br> Inhibitors:<br> -Curcumin: downregulate AKT phosphorylation and signaling.<br> -Resveratrol<br> -Quercetin: inhibit the PI3K/AKT pathway.<br> -Epigallocatechin Gallate (EGCG)<br> -Luteolin and Apigenin: inhibit AKT phosphorylation <br>
5-	AKT1	↑	v-akt murine thymoma viral oncogene homolog 1	CGL-Driver Genes	Oncogene	<b>RAC‑α serine/threonine‑protein kinase</b> (commonly referred to as AKT1) <br> It is known as the “survival kinase”. Akt mediates cell survival proliferation mainly by inhibiting the Bcl2 and MDM2 pathways, which otherwise promotes apoptosis.<br> Mechanisms of Akt1 in Cancer<br> Cell Survival: Akt1 promotes cell survival by inhibiting apoptotic pathways, allowing cancer cells to evade programmed cell death.<br> Cell Proliferation: It enhances cell cycle progression and proliferation through various signaling pathways.<br> Metabolism: Akt1 regulates glucose metabolism and lipid synthesis, supporting the metabolic demands of rapidly dividing cancer cells.<br> Angiogenesis: It promotes the formation of new blood vessels, facilitating tumor growth and metastasis.<br> <br> Akt1 is frequently activated, with its expression levels often correlating with prognosis across various cancer types.<br>
6-	Akt2	↑	RAC-beta serine/threonine-protein kinase			<b>Enzyme</b> that in humans is encoded by the AKT2 gene.<br> AKT2 is highly expressed in many human cancers, including non-small cell lung cancer (NSCLC). miR-124 overexpression can negatively regulate AKT2. knockout of both AKT1 and AKT2 will attenuate metastasis and tumor cell growth.<br>
554-	ALAT	↑	ALT, alanine aminotransferase		enzyme	<b>(or ALT)</b> -Used to be called serum glutamic-pyruvic transaminase (SGPT)<br> Most common in the liver.<br> An enzyme your body needs to break down proteins into energy.<br> It plays a crucial role in amino acid metabolism and is often measured in blood tests to assess liver function. <br> The catabolism of alanine by alanine aminotransferase 2 (ALT2) to pyruvate, was critical for the survival of non-small cell lung carcinoma (NSCLC) cells during glucose starvation. After knockdown of ALT2, cells were significantly more sensitive to glucose withdrawal compared to wildtype cells, which were rescued when supplemented with pyruvate.<br> Alanine aminotransferase (ALT) expression is highly elevated in the serum of patients with hepatocellular carcinoma.<br> A common example of dietary cancer therapy is the ketogenic diet, providing a fat-rich, low carbohydrate diet. The rationale is to reduce circulating glucose levels and induce ketosis.<br>
690-	Albumin	↓	Albumin		protein	<b>Albumin</b> is a protein found in the blood that plays a crucial role in maintaining various bodily functions, including blood volume, blood pressure, and the transport of hormones, vitamins, and minerals. <br> Associated with improved prognosis in certain types of cancer.<br> May be a marker of improved nutritional status and reduced inflammation in cancer patients.<br>
828-	ALC	↑	absolute lymphocyte count		marker	<b>ALC</b> is high in CLL
676-	ALDH	↑	Aldehyde Dehydrogenase			<b>ALDH</b> (Aldehyde Dehydrogenase) is a family of enzymes that play a crucial role in various cellular processes, including detoxification, differentiation, and cell survival. In the context of cancer, ALDH has been implicated in several aspects of tumor biology.<br> <br> ALDH enzymes are involved in the metabolism of aldehydes, which are toxic compounds that can damage cellular components. In cancer cells, ALDH enzymes can help to detoxify these compounds, promoting cell survival and resistance to chemotherapy.<br> <br> There are 19 different ALDH isoforms, and each has a distinct expression pattern in cancer. Some isoforms, such as ALDH1A1 and ALDH1A3, are more commonly associated with cancer stem cells, while others, such as ALDH2, are more widely expressed in cancer cells.<br> <br> Highly Expressed: Brain, overian, prostate, pancreatic, liver, stomach, esophageal, head and neck, melanoma, ALL, CML<br>
7-	ALDH1A1	↑	Aldehyde Dehydrogenase 1A1		Protein-coding gene	<b>(ALDH1A1)</b> is a cancer stem cell marker, and its expression correlates with prognosis in a number of malignancies. Aldehyde dehydrogenases are the cancer stem cells which plays a role in CSC progression. ALDH comprise 19 subfamilies in which ALDH1A1, ALDH1A3, ALDH3A1, ALDH5A1, ALDH7A1, and ALDH18A1 are implicated in CSC. Existing chemotherapeutic drugs eliminate the bulk of tumors but are usually not effective against CSC which express ALDH+ population. Henceforth, targeting ALDH is convincing to treat the patient's post-relapse.<br>
567-	ALDOA	↑	Aldolase A			<b>ALDOA</b> (Aldolase A) is an enzyme involved in glycolysis, the metabolic pathway that converts glucose into energy. <br> Expression level of ALDOA was significantly related to the prognosis of brain cancer, skin cancer, lung adenocarcinoma and breast cancer.<br> Aldolase enzymes, particularly ALDOA, ALDOB, and ALDOC, play a crucial role in the development and progression of cancer. While the aldolase family is mainly known for its involvement in the glycolysis pathway, these enzymes also have various pathological and physiological functions through distinct signaling pathways such as Wnt/β-catenin, EGFR/MAPK, Akt, and HIF-1α. ALDOA (Aldolase A) is an enzyme involved in glycolysis, the metabolic pathway that converts glucose into energy. <br> ALDOA is often overrepresented and has been associated with poor prognosis in various malignancies. Its expression levels can serve as potential biomarkers for tumor aggressiveness and patient outcomes.<br>
1035-	ALDOAiso2	↑	fructose-bisphosphate aldolase A isoform 2			<b>The “isoform 2” </b>designation typically points to a particular variant of ALDOA that is expressed in various tissues and can contribute to glycolytic flux. As a glycolytic enzyme, ALDOA is critical for energy production, especially under anaerobic conditions, and contributes to the metabolic reprogramming that supports rapid cell proliferation.<br>
1079-	Alix/AIP‑1	↑	Alix (ALG‑2–interacting protein X)			<b>Alix</b> (ALG‑2–interacting protein X), also known as AIP‑1, is a multifunctional protein that interacts with actin and other components of the cytoskeleton.<br> <br> – Altered expression or localization of Alix has been observed in various cancers, including breast, prostate, and colorectal cancers.<br> – Alix may contribute to tumor growth by affecting apoptosis and cell survival. In some contexts, it is suggested that Alix can modulate apoptotic signaling pathways.<br> – Studies have reported that Alix expression may be upregulated in certain tumor types, with changes in subcellular localization (e.g., increased cytoplasmic or membranous expression) linked to aggressive behavior.<br> – In some cancers, altered Alix levels have been associated with enhanced invasive and metastatic potential.<br>
8-	ALK	↑	anaplastic lymphoma receptor tyrosine kinase	CGL-Driver Genes	Oncogene	<b>Anaplastic lymphoma kinase (ALK)</b> is a member of the insulin receptor protein-tyrosine kinase superfamily.<br> ALK inhibitors, has substantially improved outcomes for patients with ALK-positive NSCLC. The common activation of ALK has led to the use of the ALK tyrosine kinase inhibitor (TKI) crizotinib.<br>
689-	ALP	↑	Alkaline Phosphatase		enzyme	<b>ALP</b> (Alkaline Phosphatase) is an enzyme found in the body, and elevated levels of ALP in the blood can be associated with various conditions, including cancer.<br> Elevated ALP: Bone, Liver, pancreatic, breast, CRC, Prostate, thyroid, kidney, GI, Neuroblastoma<br>
408-	AMACR	↑	alpha-methylacyl-CoA racemase		Protein-coding gene	<b>An enzyme</b> that in humans is encoded by the AMACR gene.<br> AMACR is a valuable diagnostic marker because of its persistent and strong expression in case of needle biopsies.<br> (AMACR) is a mitochondrial and peroxisomal enzyme that is overexpressed in prostate cancer(PCa). AMACR is frequently used as a biomarker in prostate cancer diagnosis. Its expression is typically elevated in malignant prostate tissues compared to benign tissues. The overexpression of AMACR is associated with the presence of cancer and can aid in differentiating between cancerous and non-cancerous prostate tissues.<br> Other Cancers: In colorectal and breast cancers, AMACR expression has been associated with tumor progression and may serve as a prognostic marker. Elevated AMACR levels could indicate a more aggressive tumor phenotype, leading to worse survival rates.<br>
1197-	AminoA	↑	Amino Acids			<b>Altered Amino Acid Metabolism in Cancer</b><br> • Tumors often reprogram their metabolism to meet the demands of rapid proliferation. This reprogramming includes increased uptake and utilization of certain amino acids (e.g., glutamine, serine, glycine) to support anabolic processes.<br> <br> Key Amino Acids and Their Roles<br> • Glutamine:<br> – High tumor dependency on glutamine catabolism (glutaminolysis) has been linked to aggressive phenotypes and may correlate with poor outcomes.<br> • Serine and Glycine:<br>
794-	AMP	↑	Adenosine Monophosphate		nucleotide	<b>AMP</b> (Adenosine Monophosphate) is a nucleotide that plays a crucial role in various cellular processes, including energy metabolism, cell growth, and differentiation,<br> AMP is a key energy currency in cells, serving as a intermediate in the production of ATP (Adenosine Triphosphate) from ADP (Adenosine Diphosphate).<br> AMP expression associated with Tumor growth, angiogensis, metastasis<br>
9-	AMPK	↓	adenosine monophosphate-activated protein kinase			<b>AMPK:</b> guardian of metabolism and mitochondrial homeostasis; Upon changes in the ATP-to-AMP ratio, AMPK is activated. (AMPK) is a key metabolic sensor that is pivotal for the maintenance of cellular energy homeostasis. It is well documented that AMPK possesses a suppressor role in the context of tumor development and progression by modulating the inflammatory and metabolic pathways.<br> <br> -Activating AMPK can inhibit anabolic processes and the PI3K/Akt/mTOR pathway reducing glycolysis shifting toward Oxidative Phosphorlylation.<br> <br> <br> AMPK activators:<br> -metformin or AICAR<br> -Resveratrol: activate AMPK indirectly<br> -Berberine<br> -Quercetin: may stimulate AMPK<br> -EGCG: thought to activate AMPK<br> -Curcumin: may activate AMPK <br><br> -Ginsenosides: Some ginsenosides have been associated with AMPK activation -Beta-Lapachone: A natural naphthoquinone compound found in the bark of Tabebuia avellanedae (also known as lapacho or taheebo). It has been observed to activate AMPK in certain models.<br> -Alpha-Lipoic Acid (ALA): associated with AMPK activation<br>
475-	AMPKα	↓	AMP-activated protein kinase			<b>AMPK</b> is a heterotrimeric protein complex consisting of three subunits: AMPKα, AMPKβ, and AMPKγ. AMPKα is expressed in two isoforms, AMPKα1 and AMPKα2, and these isoforms are encoded by the genes PRKAA1 and PRKAA2, respectively.<br> In many cancers, AMPKα acts as a tumor suppressor, and its downregulation is often associated with worse clinical outcomes.<br>
447-	angioG	↑	angiogenesis			<b>Process</b> through which new blood vessels.<br> Angiogenesis, the process of new blood vessel formation from pre-existing vessels, plays a crucial role in cancer progression and metastasis. Tumors require a blood supply to grow beyond a certain size and to spread to other parts of the body. <br> Vascular Endothelial Growth Factor (VEGF): VEGF is one of the most important pro-angiogenic factors. It stimulates endothelial cell proliferation and migration, leading to the formation of new blood vessels. Many tumors overexpress VEGF, which correlates with poor prognosis.<br> Hypoxia-Inducible Factor (HIF): In response to low oxygen levels (hypoxia), tumors can activate HIF, which in turn promotes the expression of VEGF and other angiogenic factors. This mechanism allows tumors to adapt to their microenvironment and sustain growth.<br>
514-	angioS	↓	angiostatin			<b>Angiostatin</b>, a key protein that suppresses angiogenesis. Angiostatin may be used in anti-angiogenesis therapy. A protein that blocks angiogenesis (the growth of new blood vessels) and is involved in blood clotting.<br> Angiostatin is a protein that is known to inhibit angiogenesis, the process by which new blood vessels form from existing ones. It is derived from the cleavage of plasminogen and has been studied for its potential role in cancer biology, particularly in relation to tumor growth and metastasis.<br> <br> Angiostatin in Cancer<br> Mechanism of Action: Angiostatin inhibits endothelial cell proliferation and migration, which are critical steps in angiogenesis. By preventing the formation of new blood vessels, angiostatin can limit the supply of nutrients and oxygen to tumors, potentially slowing their growth.<br> <br> The expression levels of angiostatin in tumors have been associated with patient prognosis in some studies. Higher levels of angiostatin may correlate with better outcomes in certain cancers, as they may indicate a more effective anti-angiogenic response. Conversely, low levels of angiostatin might be associated with poor prognosis and more aggressive disease.<br>
1073-	annexin II	↑	ANXA2			<b>Annexin II</b> belongs to the annexin family that binds phospholipids in a calcium-dependent manner.<br> <br> – Elevated levels of Annexin II have been implicated in cancer cell invasion, migration, and metastasis.<br> – High Annexin II expression is frequently associated with aggressive tumor behavior, including increased invasion, metastasis, and overall poor clinical outcomes.<br> <br> Annexin II is a significant contributor to cancer progression through its roles in cell invasion, extracellular matrix degradation, and angiogenesis. Its overexpression is frequently correlated with aggressive tumor behavior and poor prognosis, making it a promising candidate for both prognostic evaluation and as a therapeutic target.<br>
10-	AntiAg	?	Antiplatelet aggregation			<b>Antiplatelet aggregation</b> refers to the process by which platelets clump together to form a blood clot. <br> The plethora of evidence indicates that among multiple hemostasis components, platelets play major roles in cancer progression by providing surface and granular contents for several interactions as well as behaving like immune cells.On the other hand, there are suggestions that antiplatelet treatment may promote solid tumor development in a phenomenon described as “cancers follow bleeding.” The controversies around antiplatelet agents justify insight into the subject to establish what, if any, role platelet-directed therapy has in the continuum of anticancer management.<br> The interplay between antiplatelet aggregation and cancer is an area of active research, with potential implications for therapeutic strategies. Antiplatelet agents, such as aspirin, are being investigated for their role in cancer prevention and treatment, particularly in reducing metastasis and improving patient outcomes.<br>
1245-	AntiAge	↓	Anti-aging			<b>Anti-aging</b> strategies hold promise for improving overall health and potentially reducing cancer risk, the intricate interplay between the molecular mechanisms of aging and cancer requires careful consideration.<br>
813-	AntiCan	?	Anticancer Effect		general indicator	<b>Anticancer Effect</b> <br>
1103-	antiOx	↑	anti-oxidant activities			<b>Various antioxidants</b> such as Nrf2, SODs, catalase, GPxs, PRDXs, and GSTs are altered in different cancers and have been linked to prognosis. Their overexpression can correlate with aggressive tumor behavior and resistance to treatment in many contexts.<br>
913-	AntiTum	?	AntiTumor			<b>AntiTumor</b> <br>
1169-	ANXA7	↓	annexin A7			<b>NXA7</b> belongs to the annexin family of calcium-dependent phospholipid-binding proteins.<br> – It is involved in membrane trafficking, exocytosis, and cellular signal transduction.<br> – Its functions also extend to maintaining membrane integrity and participating in the regulation of intracellular calcium levels.<br> <br> – Studies have shown that ANXA7 can function as a tumor suppressor in certain contexts, where its expression is reduced in tumors relative to normal tissue.<br> – In several tumor types, particularly prostate, breast, and glioblastoma, lower ANXA7 expression has been associated with a more aggressive tumor phenotype and poorer overall prognosis.<br> – Loss or reduced expression of ANXA7 may correlate with advanced disease stage, higher rates of recurrence, and decreased survival.<br>
11-	AP-1	↑	Activator protein 1	HalifaxProj(inhibit)		<b>Transcription factor</b> that regulates gene expression in response to a variety of stimuli. Activator protein-1 (AP-1) is a transcription factor that consists of a diverse group of members including Jun, Fos, Maf, and ATF. AP-1 involves a number of processes such as proliferation, migration, and invasion in cells. Dysfunctional AP-1 activity is associated with cancer initiation, development, invasion, migration and drug resistance. , some small molecule inhibitors targeting AP-1 have been developed and tested, showing some anticancer effects.AP-1 has been described be overexpressed in many tumors, including triple-negative breast cancer (TNBC), colon cancer, classical Hodgkin’s disease, and anaplastic large cell lymphoma (ALCL).<br>
613-	APA	↑	autophagosome accumulation			<b>-Promoting cell survival:</b> Autophagosome accumulation can provide cancer cells with a means to survive under stressful conditions, such as nutrient deprivation or hypoxia.<br> -Inducing cell death: Autophagosome accumulation can lead to cell death in certain contexts, such as in response to chemotherapy or radiation therapy.<br> <br> Molecular Mechanisms:<br> mTOR Pathway: The mechanistic target of rapamycin (mTOR) is a key regulator of autophagy. Inhibition of mTOR can lead to increased autophagosome formation.<br> Beclin-1: This protein is essential for the initiation of autophagy and is often downregulated in various cancers, affecting autophagosome formation.<br> LC3 Protein: The conversion of LC3-I to LC3-II is a marker of autophagosome formation and is often studied in cancer research.<br> <br> Generally, high levels of autophagosome accumulation and autophagy-related protein expression are associated with poor prognosis in many cancers, particularly in advanced stages or in the context of treatment resistance.<br>
807-	APAF1	↓	Apoptotic Protease Activating Factor 1		protein	<b>APAF1</b> (Apoptotic Protease Activating Factor 1) is a protein that plays a crucial role in the regulation of apoptosis, or programmed cell death. APAF1 is a key component of the intrinsic pathway of apoptosis, which is activated in response to cellular stress or damage.<br> Downregulated in: breast, lung, prostate, colon (with poor prognosis)<br> APAF1 activators have been developed and are being tested in preclinical and clinical studies.<br>
12-	APC	↓	adenomatous polyposis coli	CGL-Driver Genes	TSG	<b>The APC protein</b> is a negative regulator that controls beta-catenin concentrations and interacts with E-cadherin, which are involved in cell adhesion. Mutations in the APC gene may result in colorectal cancer and desmoid tumors. The Apc protein is known to interact with several other proteins involved in signal transduction pathways, which regulate cell growth and differentiation.The Apc gene plays a key role in maintaining the integrity of the intestinal epithelium. It functions as a tumor suppressor by inhibiting the abnormal growth of cells and promoting their differentiation. Additionally, this gene helps regulate cell adhesion and migration, ensuring the proper development and function of organs and tissues.The Apc gene acts as a tumor suppressor by regulating the Wnt signaling pathway, which is essential for cell proliferation, differentiation, and self-renewal. <br> The loss of APC function can lead to dysregulation of the Wnt signaling pathway, contributing to tumorigenesis in various tissues.<br>
14-	Apoptosis	↓	Apoptosis		type of cell death	<b>Situation</b> in which a cell actively pursues a course toward death upon receiving certain stimuli.<br> Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die.<br>
1300-	APP	↑	amyloid-beta precursor protein			<b>APP</b> typically refers to the amyloid precursor protein, best known for its role in Alzheimer’s disease.<br> <br> • APP is found to be upregulated in some cancers such as certain breast cancers, colon cancers, and lung cancers. Elevated levels may influence processes such as cell proliferation, adhesion, migration, and even invasion.<br>
577-	Appetite	?	Appetite			<b>Appetite</b> <br>
15-	AR	↑	androgen receptor	HalifaxProj(suppress signaling);CGL-Driver Genes	Oncogene	<b>Androgens</b> play an important role in the proliferation, differentiation, maintenance and function of the prostate [1]. Intriguingly, they may also be involved in the development and progression of prostate cancer. Androgen deprivation therapy can suppress hormone-naïve prostate cancer, but prostate cancer changes AR and adapts to survive under castration levels of androgen.<br> <br> The prognostic significance of androgen receptor expression varies widely across different cancer types. In some cancers, high AR expression is associated with poor outcomes, while in others, it may indicate a better prognosis<br> High expression with poor prognosis is most common.<br>
392-	AR-FL	↑	full-length androgen receptor			<b>AR-FL</b> is the main therapeutic target in PCa, and the upregulated expression of this key biomarker has been reported in numerous cell line and clinical specimen, especially CRPC.<br>
393-	AR-V7	↑	androgen receptor splice variant 7			<b>Accumulating evidence</b> suggests androgen receptor splice variant 7 (AR-V7) may be associated with the prognosis of castration-resistant prostate cancer (CRPC).<br> AR-V7 is primarily studied in prostate cancer, where it has established prognostic significance. Prostate Cancer<br> Expression: AR-V7 is often overexpressed in castration-resistant prostate cancer (CRPC). Prognosis: High levels of AR-V7 are associated with poor prognosis, treatment resistance, and shorter overall survival. It is also used as a biomarker to predict response to therapies like enzalutamide and abiraterone.<br>
560-	ARG	↑	Arginases ARG1/2			<b>Arginases</b> are key enzymes that hydrolyze L-arginine to urea and L-ornithine in the urea cycle.<br> The two arginase isoforms, arginase 1 (ARG1) and arginase 2 (ARG2), regulate the proliferation of cancer cells, migration, and apoptosis; affect immunosuppression; and promote the synthesis of polyamines, leading to the development of cancer. Arginases also compete with nitric oxide synthase (NOS) for L-arginine, and their participation has also been confirmed in cardiovascular diseases, stroke, and inflammation. <br> ARG1 is a much more explored isoform of arginase localized in the cytosol and is expressed mainly in the liver.<br> ARG2, also called mitochondrial arginase, is expressed in extrahepatic tissues, i.e., the kidneys, small intestine, prostate, and mammary gland.<br> Arginases are biomarkers and can be used to track disease progression [33]. Targeting ARG1 and ARG2 has been proposed for various diseases. Currently, a dual inhibitor of arginases is under validation in clinical trials in patients with solid tumors; OATD-02 targets both extracellular and intracellular ARG1 and ARG2.<br>
16-	ARID1A	↝	AT rich interactive domain 1A (SWI-like)	HalifaxProj(activate) CGL-Driver Genes	Protein-coding gene TSG	<b>ARID1A gene</b> is involved in chromatin remodeling, a process that regulates gene expression and cell growth. The precise role of ARID1A in cancer is highly variable since ARID1A alterations can have a tumor suppressive or oncogenic role, depending on the tumor type and context. ARID1A is mutated in about 10% of all tumor types including endometrial, bladder, gastric, liver, biliopancreatic cancer, some ovarian cancer subtypes, and the extremely aggressive cancers of unknown primary. Its loss is generally associated with disease progression more often than onset. ARID1A is a significant player in cancer biology, particularly in ovarian and endometrial cancers. Its mutations are associated with poor prognosis and may influence treatment responses. <br>
17-	ARID1B	⇅	AT rich interactive domain 1B (SWI1-like)	CGL-Driver Genes	TSG	<b>ARID1B</b> is a protein encoded by a gene of the same name, involved in chromatin remodeling. Significant association exists between the nuclear expression of ARID1B and adverse prognosis in TNBC. ARID1B was highly expressed in 89 (62.7%) and poorly expressed in 53 (37.3%). ARID1A is instead overexpressed in many hepatocellular carcinomas, while the expression of this gene is reduced or lost in colorectal cancer.<br>
18-	ARID2	↓	AT rich interactive domain 2 (ARID, RFX-like)	CGL-Driver Genes	TSG	<b>ARID2</b> is a bona fide tumor suppressor gene in lung cancer. ARID2 is lost in non-small-cell lung cancer, hepatocellular carcinoma, malignant melanoma, pancreatic cancer, and colorectal cancer.<br>
585-	ARNT	↑	aryl hydrocarbon receptor nuclear translocator			<b>ARNT</b> is a protein that plays a crucial role in the regulation of gene expression in response to environmental toxins and other stimuli. ARNT is a transcription factor that forms a heterodimer with other proteins, such as the aryl hydrocarbon receptor (AhR), to regulate the expression of target genes.<br> ARNT is overexpressed in several types of cancer, including breast, lung, and colon cancer. In addition, ARNT has been shown to interact with other proteins that are involved in cancer development, such as the estrogen receptor and the androgen receptor.<br>
996-	ASC	⇅	Apoptosis-associated Speck-like protein containing a CARD			<b>ASC</b> (Apoptosis-associated Speck-like protein containing a CARD, also known as PYCARD) – ASC is a key adaptor molecule in the assembly of inflammasomes—a multiprotein complex that activates caspase-1.<br> – Beyond its inflammasome functions, ASC has been implicated in mediating apoptosis.<br> <br> – In some cancers, ASC expression is downregulated, which may impair inflammasome assembly and promote immune evasion, whereas in other tumor types, elevated ASC has been reported, sometimes reflecting a heightened local inflammatory state.<br> – Studies indicate that reduced ASC expression in certain tumor types (for example, melanoma or colon cancer) can correlate with decreased inflammasome activity, potentially leading to immune evasion and a more aggressive tumor phenotype.<br> – Conversely, in some cancers an upregulation or persistent activation of ASC-containing inflammasomes has been linked to a pro-inflammatory milieu that might drive tumor progression and metastasis.<br>
622-	ascitic	↑	ascitic fluid			<b>Ascitic fluid</b> is a type of fluid that accumulates in the abdominal cavity.<br> In cancer patients, ascitic fluid can be a sign of advanced disease. Cancer cells can spread to the abdominal cavity and produce fluid, leading to an accumulation of ascitic fluid.<br>
444-	ASCT2	↑	ASCT2 glutamine transporter			<b>Reorganization of cellular metabolism</b> is one of the hallmarks of cancer and many tumors show high glucose uptake and glutamine addiction. Glutamine is imported by the SLC family transporters from the microenvironment, and ASCT2 (encoded by the SLC1A5 gene) is recognized as a primary transporter. Of note, ASCT2 is overexpressed in different cancers and is closely related to poor prognosis.<br>
918-	ASK1	↑	Apoptosis Signal-regulating Kinase 1			<b>ASK1 (Apoptosis Signal-regulating Kinase 1)</b> is a protein kinase that plays a crucial role in cell signaling pathways, particularly in the regulation of apoptosis (programmed cell death) and cell survival.<br> ASK1 if often overexpressed and has been linked to tumor progression and poor prognosis.<br>
394-	aSmase	↓	Acid Sphingomyelinase			<b>A-SMase expression</b> correlates inversely with tumour stage in human melanoma biopsies.In melanoma, expression of acid sphingomyelinase decreases with tumor progression in both humans and mice. A-SMase expression correlates inversely with tumour stage in human melanoma biopsies.<br> <br> The SMase family includes different isoenzymes mainly distinguished by their optimal pH:<br> -Acid sphingomyelinase (aSMase):Encoded by the gene SMPD1.Functions optimally at acidic pH.<br> -Neutral sphingomyelinases (nSMases):(nSMase1, nSMase2, nSMase3) encoded by genes SMPD2, SMPD3.<br> -Alkaline sphingomyelinases: typically found in the intestinal tract.<br> <br> aSMase expression or activity is reduced compared to normal tissue. Lower aSMase activity can lead to decreased ceramide generation, potentially allowing cancer cells to avoid apoptosis.<br> <br> In many cancer-related studies where the term “SMase” is used without further specification, the discussion may center on aSMase because of its link to ceramide production and apoptosis under stress conditions (such as chemotherapy or radiotherapy).<br>
691-	AST	↑	Aspartate Aminotransferase			<b>AST (Aspartate Aminotransferase)</b> is an enzyme found in various tissues throughout the body, including the liver, heart, muscles, kidneys, and brain. Elevated levels of AST in the blood can be an indicator of tissue damage or disease.<br> AST levels can be elevated in certain types of cancer.<br>
19-	ASXL1	↓	additional sex combs like 1 (Drosophila)	CGL-Driver Genes	TSG	<b>ASXL1</b> might act as a tumor suppressor in CRC. ASXL1 is a tumor suppressor gene and its downregulation or deletion is expected to confer a growth advantage to cells.<br> ASXL1 expression loss or mutation is primarily associated with hematological malignancies, where it generally indicates a poorer prognosis. <br> Tumor Suppressor Function: ASXL1 is involved in chromatin remodeling and gene regulation, which are critical processes for maintaining normal cellular function and preventing uncontrolled cell growth. When ASXL1 is mutated or its expression is lost, it can lead to dysregulation of gene expression, contributing to tumorigenesis.<br>
1295-	ATF2	↑	Activating Transcription Factor 2			<b>ATF2 (Activating Transcription Factor 2)</b><br> -ATF2 is a member of the ATF/CREB (cyclic AMP response element‐binding protein) family of transcription factors.<br> -It functions by binding to specific DNA sequences to regulate the transcription of a variety of target genes involved in cell proliferation, stress response, apoptosis, and differentiation.<br> -ATF2 activity is regulated through phosphorylation by stress-activated protein kinases such as JNK, p38, and ERK, integrating signals from various cellular stressors.<br> <br> -Increased ATF2 activity in certain lung cancer subtypes has been linked with increased invasiveness and metastatic potential.<br>
1263-	ATF3	↑	Activating Transcription Factor 3			<b>ATF3 (Activating Transcription Factor 3)</b> is a stress‐responsive transcription factor that is frequently induced by various cellular stresses, including DNA damage, oxidative stress, and inflammatory signals.<br> <br> -Several studies have shown that ATF3 is upregulated in response to cellular stress in breast cancers.<br> -Increased ATF3 expression has been associated with reduced cell proliferation and invasiveness, suggesting a tumor-suppressive role.<br> <br> • In some cancers and contexts, elevated ATF3 is linked with apoptosis induction and a favorable prognosis, acting as a tumor suppressor.<br>
730-	ATF4	↑	Activating Transcription Factor 4		protein	<b>ATF4 (Activating Transcription Factor 4)</b> is a protein that plays a crucial role in various cellular processes, including stress response, cell growth, and differentiation.<br> ATF4 is overexpressed in several types of cancer, including breast, lung, colon, and pancreatic cancer. The overexpression of ATF4 can contribute to cancer cell growth, survival, and resistance to chemotherapy.<br> ATF4 promotes cancer cell growth by regulating the expression of genes involved in cell proliferation, angiogenesis, and metastasis. It also inhibits apoptosis (programmed cell death) by regulating the expression of anti-apoptotic genes.<br>
861-	ATF6	↑	Activating Transcription Factor 6		protein	<b>ATF6 (Activating Transcription Factor 6)</b> is a protein that plays a crucial role in the unfolded protein response (UPR), a cellular stress response pathway that is activated in response to endoplasmic reticulum (ER) stress.<br> High ATF6 expression is associated with poor prognosis, including shorter overall survival and increased risk of recurrence.<br>
485-	ATFs	↑	activating transcription factor			<b>ATFs</b> respond to extracellular signals, indicating their important roles in maintaining homeostasis. The ATF family includes ATF1, ATF2, ATF3, ATF4, ATF5, ATF6, and ATF7. Consistent with the diversity of cellular processes reported to be regulated by ATFs, the functions of ATFs are also diverse. ATFs play an important role in cell proliferation, apoptosis, differentiation and inflammation-related pathological processes.<br> <b>ATF (Activating Transcription Factor)</b> proteins are a family of transcription factors that play crucial roles in various cellular processes, including stress responses, metabolism, and cell differentiation. In the context of cancer, several ATF family members have been implicated in tumorigenesis, cancer progression, and prognosis. Here are some key points regarding ATFs and their expression in cancers with prognostic implications.<br> <b>ATF3:</b><br> Often associated with stress responses, ATF3 can have dual roles in cancer. In some contexts, it acts as a tumor suppressor, while in others, it may promote tumor growth. High expression of ATF3 has been linked to poor prognosis in certain cancers, such as breast cancer and pancreatic cancer.<br> <b>ATF4:</b><br> ATF4 is involved in the integrated stress response and can promote cell survival under stress conditions.<br> Its expression is often elevated in various cancers, including glioblastoma and multiple myeloma, and has been associated with poor prognosis due to its role in promoting survival and resistance to therapy.<br> <b>ATF6:</b><br> ATF6 is part of the unfolded protein response (UPR) and is involved in maintaining cellular homeostasis.<br> Its expression has been linked to cancer cell survival and may correlate with poor outcomes in certain malignancies.<br> <b>ATF1:</b> ATF1 is involved in regulating genes associated with cell proliferation and survival. Its expression levels can vary in different cancers, and its prognostic significance is still being explored.<br> <b>ATF2:</b><br> ATF2 has been implicated in both promoting and inhibiting cancer progression, depending on the context.<br> Elevated levels of ATF2 have been associated with poor prognosis in some cancers, such as melanoma.<br>
722-	ATG3	↑	Autophagy-related 3		protein	<b>ATG3 (Autophagy-related 3)</b> is a protein that plays a crucial role in the process of autophagy, a cellular mechanism that involves the degradation and recycling of damaged or dysfunctional cellular components. ATG3 is involved in the regulation of autophagy.<br> Increased expression in: breast, lung, GBM, ovarian, prostate, panreatic, hepatocellar.<br> Decreased expression in: colon (associated with improved prognosis).<br>
723-	ATG5	↑	Autophagy-related 5			<b>ATG5 (Autophagy-related 5)</b> is a protein that plays a crucial role in the process of autophagy, a cellular mechanism that involves the degradation and recycling of damaged or dysfunctional cellular components. ATG5 is a key component of the autophagy machinery and is involved in the formation of autophagosomes, which are double-membraned vesicles that engulf and digest cellular components.<br> Increased expression in: breast, GBM (poor prognosis).<br> Decreased in: Colon, Prostate (associated with improved prognosis).<br>
986-	ATG7	⇅	ATG7			<b>Autophagy Regulator:</b><br> – ATG7 is an E1-like enzyme crucial for the autophagy pathway.<br> – It participates in the conjugation systems that drive autophagosome formation (e.g., ATG12–ATG5 and LC3 lipidation systems).<br> <br> • Elevated Expression:<br> – In certain cancers (e.g., pancreatic cancer, some subtypes of breast cancer), ATG7 can be upregulated.<br> – Increased ATG7 expression in some contexts is thought to help tumors survive under metabolic stress by enhancing autophagy.<br> <br> • Reduced Expression or Loss-of-Function:<br> – In other contexts – for instance, in some liver cancers or specific lung cancers – reduced expression or inactivation of ATG7 has been reported.<br> – This reduction might lead to failure of effective autophagy in tumor-suppressive contexts.<br>
20-	ATM	↓	similar to Serine-protein kinase ATM (Ataxia telangiectasia mutated) (A-T, mutated); ataxia telangiectasia mutated	CGL-Driver Genes	TSG	<b>ATM</b> is considered a moderate cancer risk gene. A mutation in a moderate risk gene is just one risk factor that can contribute to cancer development. ATM has traditionally been assigned the role of a tumor suppressor. However, in both humans and mice, lymphoma and leukemia are the only clear-cut examples of cancer development caused by ATM deficiency(13). Its roles in other types of cancer, especially solid tumors, are much less clear.<br> ATM, a master regulator of DNA damage response.<br>
21-	ATP	⇅	Adenosine triphosphate			<b>Adenosine triphosphate (ATP)</b> is the source of energy for use and storage at the cellular level.<br> Cellular ATP levels are critical for cell survival, and several reports have shown that reductions in cellular ATP levels can lead to apoptosis and other types of cell death in cancer cells, depending on the level of depletion.<br> Adenosine triphosphate (ATP) is one of the main biochemical components of the tumor microenvironment (TME), where it can promote tumor progression or tumor suppression depending on its concentration and on the specific ecto-nucleotidases and receptors expressed by immune and cancer cells.<br> <br> Cancer cells, unlike normal cells, derive as much as 60% of their ATP from glycolysis via the “Warburg effect”, and the remaining 40% is derived from mitochondrial oxidative phosphorylation.<br>
1199-	ATP:AMP	↝	ATP:AMP ratio			<b>ATP/AMP ratio</b>, a good indicator of cellular energy charge.<br> A high ratio signifies energy abundance, whereas a low ratio indicates energy stress.<br> <br> – Cancer cells often shift their metabolism toward glycolysis even in the presence of oxygen, a phenomenon that can lead to abnormal ATP/AMP ratios.<br> – An increased reliance on glycolysis may lead to a lower ATP production efficiency compared to oxidative phosphorylation, potentially lowering the ATP/AMP ratio despite high rates of glucose metabolism.<br> • Activation of Energy-Sensing Pathways<br> – A decreased ATP/AMP ratio activates AMPK, which in turn can inhibit anabolic pathways (e.g., mTOR signaling) that promote cell growth.<br>
364-	ATPase	?	ATPase (V‐ATPase)			<b>Vacuolar ATPase (V‐ATPase)</b> is an ATP‐dependent H+‐transporter that pumps protons across intracellular and plasma membranes. V-ATPase inhibition reduces in vitro invasion and migration of a variety of cancer cell types and that the pump is involved in signaling, growth, survival, and drug resistance of cancer cells.<br>
717-	ATR	↑	Ataxia-Telangiectasia and Rad3-related			<b>ATR (Ataxia-Telangiectasia and Rad3-related)</b> is a serine/threonine kinase that plays a crucial role in maintaining genome stability and preventing cancer.<br> <br> ATR is a protein kinase that is activated in response to DNA damage, particularly replication stress and single-strand breaks. When DNA damage occurs, ATR is activated and phosphorylates a variety of downstream targets, including Chk1, p53, and BRCA1. This activation of ATR triggers a signaling cascade that leads to cell cycle arrest, DNA repair, and apoptosis (programmed cell death) if the damage is too severe to be repaired.<br> ATR is frequently overexpressed in cancers, and its expression is associated with a more aggressive disease and poorer outcomes.<br>
22-	ATRX	↓	alpha thalassemia/mental retardation syndrome X-linked (RAD54 homolog, S. cerevisiae)	CGL-Driver Genes	TSG	<b>ATRX</b> is one of the most frequently mutated tumor suppressor genes in human cancers. ATRX protein is a chromatin remodeler and transcriptional regulator that is essential for normal development. ATRX loss in gliomas has been demonstrated to promote ALT. ATRX absence has also been strongly linked to DNA damage and replicative stress [9]. ATRX loss may occur by mutations, deletions, or gene fusions and correlates with other defined molecular changes such as the ALT phenotype, PDGFRA (platelet-derived growth factor receptor alpha) amplification, and TP53 (tumor protein P53) mutation [10].<br>
637-	autolysosome	?	autolysosome			<b>Autolysosomes</b> are organelles involved in the process of autophagy, a cellular mechanism that degrades and recycles damaged or dysfunctional cellular components. <br> Autolysosomes, specifically, are involved in the final stages of autophagy, where the autophagosome fuses with a lysosome to form an autolysosome. The autolysosome then degrades the engulfed cellular components, releasing the resulting nutrients back into the cell.<br>
809-	autoS	?	autoschizis		cell death	<b>Autoschizis</b> is a process of cell death that is distinct from apoptosis and necrosis. It is characterized by the self-destruction of a cell through a series of cellular changes, including the formation of vacuoles, the breakdown of cellular organelles, and the eventual fragmentation of the cell.<br>
1088-	AVOs	↓	Acidic vesicular organelles			<b>Acidic vesicular organelles (AVOs)</b> are cellular compartments that are characterized by their low pH and include lysosomes, autophagosomes, and autolysosomes. They play a central role in several cellular processes, including degradation of intracellular components, recycling of cellular constituents, and autophagy.<br> <br> Autophagy and Its Role in Cancer<br> Cell Survival Mechanism:<br> Autophagy is often activated under stressful conditions such as nutrient deprivation, hypoxia, or chemotherapy. By degrading and recycling damaged proteins and organelles, autophagy helps cancer cells survive under adverse conditions.<br> Tumor Suppressor Function:<br> In early stages of tumorigenesis, autophagy can limit genomic instability and inflammation by removing damaged organelles and misfolded proteins. Thus, it can act as a barrier to malignant transformation.<br> Tumor Promotion:<br> In established tumors, autophagy may support cancer cell survival. Enhanced autophagy can provide energy and metabolic substrates, thereby facilitating tumor growth and resistance to therapy.<br>
23-	AXIN1	↓	Axis inhibition protein 1	CGL-Driver Genes	TSG	<b>AXIN1</b> is a tumor suppressor and a crucial negative regulator of the Wnt/β-catenin signaling pathway. Abnormal expression of AXIN1 protein has been shown to be associated with various tumors, including CRC.<br> Axin1 Protein expression was decreased remarkably in tumor specimens when compared to normal tissues. Alterations of Axin1 including AXIN1 gene mutations and decreased Axin1 expression have been reported in several types of solid tumors.<br>
976-	Axin2	↑				<b>Axin2</b> is a key component of the Wnt/β-catenin signaling pathway, acting primarily as a negative feedback regulator. Its expression is often used as a readout for active Wnt signaling, which in many cancers is involved in tumor initiation, progression, and cancer stem cell maintenance. <br> <br> Axin2 is frequently upregulated, reflecting high Wnt/β-catenin activity.<br>
802-	AXL	↑	Anexelekto			<b>AXL (Anexelekto)</b> is a receptor tyrosine kinase that plays a crucial role in the regulation of cell growth, survival, and migration. <br> AXL is involved in the regulation of cell growth and survival, and its overexpression has been linked to the development of cancer.<br> AXL works by binding to its ligand, growth arrest-specific protein 6 (GAS6), which activates the AXL receptor and triggers a signaling cascade that promotes cell growth and survival.<br> AXL can also interact with other proteins, including PI3K and AKT, to regulate cell growth and survival.<br>
24-	B2M	?	beta-2-microglobulin	CGL-Driver Genes	TSG	<b>High B2M expression</b> correlated with worse prognosis. Our results indicate that B2M and HLA-A loss occurs frequently in tumors.<br> B2M is considered a tumor suppressor gene.<br>
647-	BACH1	↑	BTB and CNC homology 1			<b>Bach1 (BTB and CNC homology 1)</b> is a protein involved in the regulation of gene expression, specifically through the control of the stability and translation of messenger RNA (mRNA).<br> Bach1 has been found to be overexpressed in several types of cancer, including lung, breast, and prostate cancer. High levels of Bach1 have been associated with increased cancer cell proliferation, migration, and invasion, as well as reduced sensitivity to chemotherapy.<br>
591-	Bacteria	?	Effect on Bacteria			<b>Effect on Bacteria</b> <br>
426-	BAD	↑	BCL2 associated agonist of cell death			<b>BCL2 associated agonist of cell death (BAD)</b> protein is a pro-apoptotic member of the Bcl-2 gene family.<br> Expression of the BAD is associated with the development and progression of cancer.<br>
632-	Bak	↓	BAK or BAK1			<b>Bak (also known as BAK or BAK1)</b> is a protein that plays a crucial role in regulating cell death.<br> In cancer, the Bak protein is often inactivated or downregulated, allowing cancer cells to evade apoptosis and continue to proliferate uncontrollably.<br>
25-	BAP1	↓	BRCA1 associated protein-1 (ubiquitin carboxy-terminal hydrolase)	CGL-Driver Genes	TSG	<b>BAP1</b> is the most frequently mutated deubiquitinase in human cancers and is a major tumor suppressor.BRCA-1 associated protein 1 (BAP1) is a tumor suppressor gene that has been implicated in the pathogenesis of several malignancies.<br> Normal fibroblast cell cultures in individuals with heterozygous loss of BAP1 exhibited increased glycolysis and decreased aerobic mitochondrial respiration. <br>
26-	BAX	↓	Apoptosis regulator BAX		Proapototic protein	<b>BAX</b> is a member of the Bcl-2 gene family.<br> Pro-apoptotic protein that forms heterodimers with anti-apoptotic BCL2 proteins; involved in various cellular activities and regulated by p53; mediates the release of cytochrome c from mitochondria.<br>
352-	Bax:Bcl2	↓	Bax:Bcl2 ratio			<b>Bax and Bcl-2</b> are the major members of Bcl-2 family that play a key role in tumor progression or inhibition of intrinsic apoptotic pathway triggered by mitochondrial dysfunction. <br> Bax/Bcl-2 ratio is typically significantly lower in tumors.<br>
1123-	BBB	∅	Blood-Brain Barrier			<b>Blood-Brain Barrier(BBB)</b> is a term often used regarding if a product has the ability to cross the BBB.<br>
583-	BCAP	↑	B cell adaptor for phosphatidylinositol 3(PI3)-kinase (BCAP)			<b>BCAP (B-cell adaptor for phosphoinositide 3-kinase)</b> expression has been studied in various types of cancer, particularly in B-cell malignancies.<br> BCAP is primarily expressed in B-cells, and its expression levels can be altered in B-cell malignancies such as chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), and other lymphomas.<br> BCAP is involved in the PI3K signaling pathway, which is crucial for cell growth, survival, and metabolism. <br> Some studies suggest that BCAP may be involved in the signaling pathways that affect tumor growth and metastasis. High BCAP expression could correlate with poor prognosis in certain subtypes of breast cancer.<br>
27-	Bcl-2	↑	B-cell CLL/lymphoma 2	HalifaxProj (inhibit) CGL-Driver Genes	Antiapoptotic Oncogene	<b>The proteins of BCL-2 family</b> are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL, the pro-apoptotic proteins represented by BAX and Bak, and the pro-apoptotic BH3-only proteins represented by BAD and BID.<br> Since the expression of Bcl-2 protein in tumor cells is much higher than that in normal cells, inhibitors targeting it have little effect on normal cells.<br>
28-	Bcl-xL	↑			pro-survival proteins	<b>The proteins of BCL-2</b> family are classified into three subgroups, i.e., the anti-apoptotic/pro-survival proteins represented by BCL-2 and BCL-XL.<br> BCL-XL overexpressing cells exhibited higher tumors sphere formation capacity and expressed higher levels of some stem cell markers, supporting the concept that BCL-XL plays essential roles in the maintenance of cancer stem cell phenotype.<br>
29-	BCOR	↓	BCL6 co-repressor	CGL-Driver Genes	TSG	<b>(BCOR)</b> is a transcription factor involved in the control of embryogenesis, mesenchymal stem cells function, hematopoiesis, and lymphoid development. <br> (BCOR) is a tumor suppressor gene.<br> BCOR is recognized as a tumor suppressor gene, and its inactivation or mutation is linked to the development and progression of several types of cancers.<br>
503-	BCR	?	Breakpoint Cluster Region		Gene	<b>The term "Breakpoint Cluster Region" (BCR)</b> is often associated with a specific gene located on chromosome 22, which is involved in certain types of cancer, particularly chronic myeloid leukemia (CML). The BCR gene is known for its role in the formation of the BCR-ABL fusion protein, which results from a translocation between chromosome 9 and chromosome 22 (specifically, the Philadelphia chromosome.<br>
1075-	BCR-ABL	↑				<b>BCR‑ABL</b> is a well‐characterized fusion oncoprotein resulting from a chromosomal translocation that has significant diagnostic, prognostic, and therapeutic relevance in hematologic malignancies.<br> <br> – It promotes uncontrolled cell proliferation, inhibits apoptosis, and contributes to genomic instability.<br> – Quantitative measurement of BCR‑ABL transcript levels is used to monitor minimal residual disease (MRD) and predict response to therapy.<br> <br> – BCR‑ABL is not only a diagnostic hallmark of CML and certain ALL cases but also a critical driver of disease progression that can be effectively targeted by molecular therapies.<br>
30-	Beclin-1	↓	Beclin-1		Protein Coding gene	<b>Beclin 1</b>, an autophagy and haploinsufficient tumor-suppressor protein, is frequently monoallelically deleted in breast and ovarian cancers. However, the precise mechanisms by which Beclin 1 inhibits tumor growth remain largely unknown.<br> A key biomarker of autophagy is Beclin-1. Beclin-1 stimulates LC3-I’s lipidation to produce LC3-II, which localizes to the autophagosome membrane to activate the development of autophagosomes.<br>
981-	Bfl-1	↑	Bfl-1 (A1)			<b>Bfl-1</b> (also known as A1 in some contexts) in the context of cancer biology, its role in apoptosis regulation, and its relevance to immunotherapy.<br> • Bfl-1 is a member of the BCL2 protein family, which comprises both pro- and anti-apoptotic regulators.<br> • Also known as A1 in several species, Bfl-1 is an anti-apoptotic protein that contributes to cell survival by binding and sequestering pro-apoptotic factors.<br> • This interaction helps prevent the initiation of the mitochondrial (intrinsic) pathway of apoptosis.<br> <br> <br> – Several studies have found that Bfl-1 can be overexpressed in various malignancies.<br> – Its increased expression allows cancer cells to resist apoptosis induced by both intrinsic cellular stress and extrinsic signals, contributing to tumor development and progression.<br>
1162-	BG	?	Blood Glucose			<b>Blood Glucose</b><br>
466-	BID	↓	BH3 interacting-domain death agonist		pro-apoptotic protein	<b>Bid</b> is an abundant pro-apoptotic protein of the Bcl-2 family that is crucial for death receptor-mediated apoptosis in many cell systems.<br> The expression of BID can serve as a prognostic marker in several cancers. Higher levels of BID are often associated with increased apoptosis and better treatment responses, while lower levels may indicate resistance to therapy and poorer outcomes.<br> <br> Generation of Truncated Bid (tBid):<br> • When apoptosis is signaled, specific proteases (such as caspase-8) cleave full-length Bid into its truncated form, tBid.<br> • tBid is the active form that translocates to mitochondria.<br> <br> So "the truncation of Bid" means that the protein has been converted into an active form (tBid) that supports apoptosis.<br>
483-	BIM	↓	BIM protein (BCL-2 Interacting Mediator of cell death)			<b>A pro-apoptotic protein</b> that plays a crucial role in regulating cell death, particularly in the context of cancer. BIM is a member of the BCL-2 family of proteins, which are key regulators of apoptosis (programmed cell death).<br> BIM cancer is characterized by the overexpression of the BIM protein, which is a pro-apoptotic protein that promotes cell death.<br> BIM protein has been shown to have both tumor-suppressive and tumor-promoting roles, depending on the context.<br> High BIM expression: Melanoma, lung, breast, colorectal.<br> Low BIM expression: Leukemia, Lymphoma, Prostate<br> The expression of BIM can serve as a prognostic marker in several cancers. Higher levels of BIM are often associated with increased apoptosis and better treatment responses, while lower levels may indicate resistance to therapy and poorer outcomes.<br>
792-	BioAv	?	bioavailability		measurement	<b>Bioavailability</b> (usually in %) absorbed by the body.<br>
1310-	BioEnh	?	bioenhancer			<b>A bioenhancer</b> is an agent capable of enhancing bioavailability and efficacy of a drug with which it is co-administered<br> <br> <a href="https://nestronics.ca/dbx/tbResList.php?tsv=1310&wNotes=on&exSp=open"> Query Database for BioEnhancers </a> but the bioenhancers mainly show up under the target notes <br> <br> <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3657948/pdf/IJABMR-1-5.pdf"> Bioenhancers </a><br> - piperine and quercetin are considered bio-enhancers<br> - genistein<br> Piperine act by suppressing P-gp and cytochrome P450 enzymes, which counteract the metabolism of rifampicin via these proteins, thus enhancing the oral bioavailability of rifampicin. It also decreases the intestinal production of glucuronic acid, thus allowing more substances to enter the body in active form. It was found to increase the bioavailability of various drugs from 30% to 200%.[25]<br> Table 1: Published research on bioenhancer effect of piperine with various medicines<br> Drug Studied in Reference<br> Antimicrobial agents<br> Rifampicin In vitro Balakrishnan et al, 2001[11]<br> Isoniazid Rabbits Karan et al, 1998 [12]<br> Pefl oxacin Mountain Gaddi goats Madhukar et al, 2008[13]<br> Tetracycline Rats Atal et al, 1980[14]<br> Sulfadiazine Rats and dogs Atal et al, 1980[14]<br> Oxytetracycline Poultry birds Singh et al, 2005[15]<br> Ampicillin Rabbits Janakiraman and Manavalan, 2008[16]<br> Norfl oxacin Rabbits Janakiraman and Manavalan, 2008 [16]<br> Nevirapine Adult males Kasibhatta et al, 2007 [17]<br> Metronidazole In vitro Singh et al, 2010[18]<br> Analgesics<br> Diclofenac sodium Albino mice Pooja et al, 2007[19]<br> Pentazocine Albino mice Pooja et al, 2007[19]<br> Nimesulide Mice Gupta et al, 1998[20]<br> Antiepileptics<br> Carbamazepine In vitro Pattanaik et al, 2009 [21]<br> Phenytoin Human volunteers Bano et al, 1987[22]<br> Pentobarbitone Rats Majumdar et al, 1990[23]<br> Other drugs<br> Propranolol In vitro Bano et al, 1991 [24]<br> Theophylline In vitro Bano et al, 1991 [24]<br> Nutrients In vitro Pooja et al, 2007 [19 <br> ***Borneol<br> -Borneol is thought to temporarily open tight junctions between endothelial cells, enhancing drug penetration. It may also downregulate efflux transporters such as P-glycoprotein (P-gp), allowing higher intracellular concentrations of co-administered drugs. <br> <br> -presence of urea (as a carrier) increased the aqueous solubility of capsaicin by 3.6-fold compared to pure capsaicin<br> <br> Quercetin is found in citrus fruits and is a dual inhibitor of cytochrome P 3A4 (CYP3A4) and P-gp. <br> Table 2: Effect of quercetin pretreatment/co-treatment on pharmacokinetic parameters of different drugs<br> Drugs combined Increase in pharmacokinetic parametera<br> Cmax AUC ABA<br> Verapamil Two fold Two fold SH<br> Diltiazem SH SH Not known<br> Paclitaxel SH SH T wo fold<br> Digoxin 413% 170% Not known<br> Tamoxifen SH SH 59%<br> Compared to drug in question alone. Cmax, peak plasma concentration; AUC, area under the curve; ABA, absolute bioavailability; SH, significantly higher.<br> <br> Another flavonoid, genistein belongs to the isoflavone class of flavonoids. It is a well-known phytoestrogen. The presence of genistein (10 mg/kg) caused an increase in AUC (54.7%) and a decrease in the total plasma clearance (35.2%) after oral administration of paclitaxel at a dose of 30 mg/kg in rats.[37]<br> Naringin is the major flavonoid glycoside found in grapefruit and makes grapefruit juice taste bitter. Oral naringin (3.3 and 10 mg/kg) was pretreated 30 min before and after intravenous administration of paclitaxel (3 mg/kg), the AUC was significantly improved (40.8% and 49.1% for naringin doses of 3.3 and 10 mg/kg, respectively).[38<br> <br> Carum carvi/Cuminum cyminum ( Jeera)<br> Carum carvi seeds are a prized culinary herb. Extracts of its parts increased significantly (25%–300%), the bioavailability of a number of classes of drugs, such as antibiotics, antifungals, antivirals, anticancer, cardiovascular, anti-inflammatory/ antiarthritic, anti-TB, antileprosy, antihistaminic/respiratory disorders, corticosteroids, immunosuppressants, and antiulcers. Such extracts either in the presence or absence of piperine have been found to be highly selective in their bioavailability/bioefficacy-enhancing action.[40]<br> Capmul<br> One of the widely used bioenhancers is Capmul MCM C10, a glyceryl monocaprate, produced from edible fats and oils and is commonly used in lip products. In a study in rats, antibiotic ceftriaxone when given concomitantly with capmul, increased the bioavailability of ceftriaxone by 80%.[41] <br> Nitrile glycoside <br> Nitrite glycoside is a bioenhancer for drugs and nutrients. Novel bioactive nitrile glycosides, niaziridin and niazirin is obtained from the leaves, pods, and bark of Moringa oleifera. [42] An immunoenhancing polysaccharide and niaziminin, having structural requirement to inhibit tumor promoter-induced Epstein–Barr virus activation have been reported from the leaves of Moringa.[43,44] It enhances the bioactivity of commonly used antibiotics, such as rifampicin, tetracycline, and ampicillin, and also facilitate the absorption of drugs, vitamins, and nutrients through the gastrointestinal membrane, thus increasing their bioavailability. [41] Niazirin is another bioactive nitrile glycoside belonging to M. oleifera. [45,46] Process of isolation of nitrite glycoside from M. oleifera has been patented (US 6858588) by Khanuja et al in 2004–2005. [42<br> <br> Mechanism of Action Of Bioenhancers<br> Bioavailability-enhancing activity of natural compounds from the medicinal plants may be attributed to various mechanisms, such as P-gp inhibition activity by flavone, quercetin, and genistein; [51] inhibition of efflux transporters, such as P-gp and breast cancer resistance protein (BCRP),[52,53] by naringin and sinomenine thus preventing drug resistance; DNA receptor binding, modulation of cell signaling transduction, and inhibition of drug efflux pumps[54-56] ; by stimulating leucine amino peptidase and glycyl–glycine dipeptidase activity, thus modulating the cell membrane dynamics related to passive transport mechanism as seen with piperine [57] ; nonspecific mechanisms, such as increased blood supply to the gastrointestinal tract, decreased hydrochloric acid secretion, preventing breakdown of some drugs[6] ; and inhibition of metabolic enzymes participating in the biotransformation of drugs, thus preventing inactivation and elimination of drugs and thereby, increasing their bioavailability. [57-5]<br>
1248-	BMAL1	⇅	ARNTL			<b>BMAL1 (Brain and Muscle ARNT-Like 1)</b>, also known as ARNTL, is a core component of the circadian clock machinery. It regulates daily rhythmicity in gene expression, metabolism, cell cycle, and DNA repair mechanisms.<br> <br> -BMAL1 is emerging as an important factor in cancer biology through its regulation of circadian rhythms, metabolism, and the cell cycle. Altered BMAL1 expression or disrupted oscillatory patterns have been associated with more aggressive tumors and poorer prognosis in several cancer types, including breast, colorectal, lung, and liver cancers.<br>
538-	BMD	↓	bone mineral density			<b>The Bone Mineral Density (BMD)</b> Test is a diagnostic tool used to measure the density and strength of bones. A bone mineral density (BMD) test measures calcium and other minerals in bone. Cancer treatments, including chemotherapy, hormone therapy, and radiation, can negatively impact bone health and lead to decreased BMD, increasing the risk of osteoporosis and fractures.<br> Some studies suggest that low BMD may be associated with poorer survival outcomes in certain cancer types, although the relationship can be complex and influenced by various factors.<br>
837-	BMI1	↑	B cell-specific Moloney murine leukemia virus integration site 1			<b>BMI1</b> (B cell-specific Moloney murine leukemia virus integration site 1) is a protein that plays a crucial role in the regulation of cell growth, differentiation, and survival. It is a key component of the Polycomb repressive complex 1 (PRC1), which is involved in the silencing of genes through histone modification.<br> Overexpression of BMI1 has been observed in many types of cancer, and it is often associated with poor prognosis and reduced survival rates.<br>
777-	BMP2	↑	Bone Morphogenetic Protein 2			<b>BMP2</b> (Bone Morphogenetic Protein 2) is a member of the TGF-β (Transforming Growth Factor-beta) superfamily, which plays a crucial role in regulating cell growth, differentiation, and apoptosis. <br> BMP2 is overexpressed in: Osteosarcoma, breast, lung, prostate cancers.<br>
916-	BMP3	↓	Bone Morphogenetic Protein 3			<b>Bone Morphogenetic Protein 3 (BMP3)</b> is a member of the TGF-β superfamily, which plays a crucial role in regulating cell growth, differentiation, and apoptosis.<br> <br> Tumor Suppressor Role<br> Expression: BMP3 has been identified as a potential tumor suppressor in various cancers. Its expression can be downregulated in several malignancies, which may contribute to tumor progression. Prognosis: Low levels of BMP3 expression have been associated with poor prognosis in certain cancers, including colorectal cancer and gastric cancer. Restoration of BMP3 expression in cancer cells has been shown to inhibit cell proliferation and induce apoptosis.<br>
512-	BMPs	⇅	Bone morphogenetic protein			<b>BMPs</b> are important cytokines belonging to the Transforming Growth Factor (TGF)-β superfamily. BMP2 is highly overexpressed in human non-small cell lung cancer (NSCLC) and correlates with tumor stage and metastatic burden. BMP-2 level from patients with bone metastasis is significantly higher compared to patients without bone metastasis.<br> BMPs display significantly higher expression in tumors, which have been used as new biomarkers for the prognosis of cancer patients.<br> However, some data revealed an opposite role of BMP signaling in tumors. BMP-10 was downregulated in gastric cancer samples. BMP-6 expression was also absent in breast cancer tissues and might suppress breast cancer metastasis.<br>
1125-	BNIP3	↑	BCL2/adenovirus E1B interacting protein 3			<b>BNIP3</b> (BCL2/adenovirus E1B interacting protein 3) is a mitochondrial pro‐apoptotic protein that also plays a key role in hypoxia‐induced autophagy and mitophagy. Its expression in tumors has attracted attention because it can influence cancer cell survival under stress, and its expression level has been linked to prognosis in several cancer types.<br> <br> BNIP3 is frequently overexpressed in cancers characterized by significant hypoxia and has been linked to poorer outcomes in pancreatic, breast, lung, colorectal, and brain cancers. However, its exact role can vary; therefore, while BNIP3 is a promising prognostic biomarker in many contexts, its clinical utility may improve when evaluated alongside other hypoxia and autophagy markers.<br> <br> BNIP3 which is a protein stimulated by ROS and promotes apoptosis.<br>
609-	BNP	↑	Brain Natriuretic Peptide			<b>Brain Natriuretic Peptide</b> is a hormone produced by the heart, and it plays a crucial role in regulating blood pressure and fluid balance in the body.<br> BNP may be involved in the regulation of hormones that promote tumor growth.<br> BNP is expressed in various types of cancer, including: Breast, Lung, Colorectal, Prostate.<br>
1018-	BOK	↓	Bcl-2-related ovarian killer			<b>BOK</b> (Bcl-2-related ovarian killer) is a member of the Bcl-2 family of proteins and is generally considered a pro-apoptotic factor.<br> <br> BOK is categorized as a pro-apoptotic protein and is thought to contribute to the intrinsic (mitochondrial) pathway of apoptosis.<br> <br> Although direct targeting of BOK is not yet well established, restoring or enhancing its expression in tumors with low BOK levels could be a strategy to re-sensitize cancer cells to apoptosis.<br> <br> Alterations in BOK expression have been observed in several types of cancers. In some tumor models, downregulation or loss of BOK expression may be associated with reduced apoptotic response, which can contribute to uncontrolled cell survival.<br>
580-	BowelM	?	Regular Bowel Movement			<b>Regular Bowel Movement</b> <br>
592-	BP	?	Blood Pressure			<b>Blood Pressure</b><br>
31-	BRAF	↑	v-raf murine sarcoma viral oncogene homolog B1	CGL-Driver Genes	Oncogene	<b>BRAF</b> is a gene involved in controlling cell growth.<br> BRAF mutations are present in approximately 10%-15% of colorectal cancers, 35% of melanomas, and more than 50% of thyroid papillary carcinomas. The majority of BRAF mutations are V600E mutations. the v-Raf murine sarcoma viral oncogene homolog B1 (BRAF) gene mutation has been observed in esophageal cancer and is associated with poor prognosis.<br> It encodes a protein that is part of the RAS-RAF-MEK-ERK signaling pathway, which is involved in regulating cell division, differentiation, and survival. When BRAF is mutated, particularly in the form of the BRAF V600E mutation, it can lead to constitutive activation of the signaling pathway, promoting uncontrolled cell growth and contributing to the development of various cancers, most notably melanoma.<br>
32-	BRCA1	↓	BReast CAncer gene 1	CGL-Driver Genes	TSG	<b>BRCA1 and BRCA2</b> are tumor suppressor genes, which, when they function normally, keep tumors from forming.<br> BRCA1 mutations are associated with an increased risk for:<br> Breast cancer, including an aggressive form called Triple Negative Breast Cancer<br> Ovarian cancer<br> Pancreatic cancer<br> Prostate cancer<br>
33-	BRCA2	↓	BReast CAncer gene 2	CGL-Driver Genes	TSG	<b>BRCA1 and BRCA2</b> are tumor suppressor genes, which, when they function normally, keep tumors from forming.<br> BRCA2 mutations are associated with an increased risk for:<br> Breast cancer<br> Ovarian cancer<br> Melanoma<br> Pancreatic cancer<br> Prostate cancer<br>
575-	breath	?	breathing ability			<b>Breathing ability</b><br>
451-	BRG1	↓	Brahma-related gene 1			<b>Brahma-related gene 1</b>, also known as SMARCA4.<br> BRG1 is one of two catalytic subunits of the SWI/SNF ATP-dependent chromatin-remodeling complex. In cancer, it has been hypothesized that BRG1 acts as a tumor suppressor.<br> BRG1 is often found to be mutated or downregulated in cancer (NSCLC). Loss of BRG1 expression is associated with poor prognosis and may contribute to tumor progression.<br> BRG1 serves as a potential biomarker for prognosis in various cancers, but its role can be context-dependent.<br>
1045-	Brk/PTK6	↑	Breast Tumor Kinase/Protein Tyrosine Kinase 6			<b>Breast Tumor Kinase (BrK)</b>, also known as Protein Tyrosine Kinase 6 (PTK6).<br> BrK is involved in intracellular signaling, influencing pathways related to cell proliferation, migration, and differentiation.<br> – In normal tissues, its expression is often limited; however, aberrant expression in tumors may contribute to oncogenic processes, including enhanced cell survival and metastatic potential.<br> – The kinase modulates key signaling cascades such as PI3K/AKT and MAPK that drive tumor progression.<br> <br> BrK is most widely studied in breast cancer where it is frequently overexpressed, especially in a subset of tumors that do not express classical receptors (e.g., triple-negative breast cancers) as well as in some hormone receptor–positive cases.<br> High BrK expression has been linked in several studies to enhanced tumor progression, increased metastasis, and a poorer overall survival.<br>
1115-	BTG3	↓	B-cell translocation gene 3		tumor suppressor gene	<b>BTG3</b> (B-cell translocation gene 3) is considered a tumor suppressor gene involved in cell cycle regulation, apoptosis, and differentiation.<br> <br> -BTG3 belongs to the BTG/Tob family of anti-proliferative genes and plays a role in cell cycle regulation by inhibiting cell proliferation and promoting differentiation.<br> <br> -Several studies have reported reduced expression or loss of BTG3 in different tumor types, including lung, breast, prostate, ovarian, and colorectal cancers.<br> -Low BTG3 levels have been correlated with higher tumor grade, increased metastasis, and advanced clinical stage.<br>
37-	CA	↑	Carbonic anhydrases			<b>Family of enzymes</b> that catalyze the reversible hydration of carbon dioxide (CO₂) to bicarbonate (HCO₃⁻) and a proton (H⁺).<br> Carbonic Anhydrase IX (CAIX) is a well-described enzyme in renal cell carcinoma, with its expression being regulated by the hypoxia-inducible factor 1 alpha, it is known for interfering with hypoxia processes.<br> Carbonic anhydrase 9 (CA9) is a protein to be upregulated under exposure to hypoxic conditions. Hypoxic conditions are known to be associated with resistance to chemotherapy and radiotherapy, and with poor cancer prognosis. <br> Of the carbonic anhydrases, CA9 and CA12, are transmembrane isozymes that are highly expressed in some tumours, and may be implicated in acidification of the extracellular milieu surrounding cancer cells, thus creating a microenvironment conducive to tumour growth and spread.<br> Carbonic anhydrase IX, is an endogenous marker for hypoxia.<br>
38-	Ca+2	↑	Calcium Ion Ca+2			<b>In all eukaryotic cells</b>, intracellular Ca2+ levels are maintained at low resting concentrations (approximately 100 nM) by the activity of the major Ca2+ extrusion system, the plasma membrane Ca2+-ATPase (PMCA), which exchanges extracellular protons (H+) for cytosolic Ca2+.<br> Indeed, sustained elevation of [Ca2+]C in the form of overload, saturating all Ca2+-dependent effectors, prolonged decrease in [Ca2+]ER, causing ER stress response, and high [Ca2+]M, inducing mitochondrial permeability transition (MPT), are considered to be pro-death factors.<br> In cancer the Ca2+-handling toolkit undergoes profound remodelling (figure 1) to favour activation of Ca2+-dependent transcription factors, such as the nuclear factor of activated T cells (NFAT), c-Myc, c-Jun, c-Fos that promote hypertrophic growth via induction of the expression of the G1 and G1/S phase transition cyclins (D and E) and associated cyclin-dependent kinases (CDK4 and CDK2).<br> Thus, cancer cells may evade apoptosis through decreasing calcium influx into the cytoplasm. This can be achieved by either downregulation of the expression of plasma membrane Ca2+-permeable ion channels or by reducing the effectiveness of the signalling pathways that activate these channels. Such protective measures would largely diminish the possibility of Ca2+ overload in response to pro-apoptotic stimuli, thereby impairing the effectiveness of mitochondrial and cytoplasmic apoptotic pathways.<br> Voltage-Gated Calcium Channels (VGCCs): Overexpression of VGCCs has been associated with increased tumor growth and metastasis in various cancers, including breast and prostate cancer.<br> Store-Operated Calcium Entry (SOCE): SOCE mechanisms, such as STIM1 and ORAI1, are often upregulated in cancer cells, contributing to enhanced cell survival and proliferation.<br> High intracellular calcium levels are associated with increased cell proliferation and migration, leading to a poorer prognosis. Calcium signaling can also influence hormone receptor status, affecting treatment responses.<br> Increased Ca²⁺ signaling is associated with advanced disease and metastasis. Patients with higher CaSR expression may have a worse prognosis due to enhanced tumor growth and resistance to apoptosis. -Ca2+ is an important regulator of the electric charge distribution of bio-membranes.<br>
1176-	CA125	↑	CA125			<b>CA125</b> is a protein that is often measured in the blood as a tumor marker, primarily in the context of ovarian cancer.<br> <br> -CA125 is most commonly used to monitor treatment response in patients already diagnosed with ovarian cancer and to detect its recurrence.<br> -It may be elevated in many cases of ovarian cancer, especially the epithelial type, making it a useful marker in certain clinical settings.<br>
1016-	cachexia	↑	cachexia			<b>Cachexia</b> is a complex metabolic syndrome characterized by severe body weight, muscle, and fat loss that cannot be fully reversed by conventional nutritional support.<br> It is commonly associated with advanced cancers, including pancreatic, lung, gastrointestinal, and head and neck cancers.<br> <br> Cachexia can lead to significant fatigue, decreased muscle strength, and overall physical debilitation, severely affecting a patient’s quality of life and functional status.<br>
471-	CAFs/TAFs	↑	cancer/tumor-associated fibroblast			<b>Also known as tumour-associated fibroblast TAF</b><br> A cell type within the tumor microenvironment that promotes tumorigenic features by initiating the remodelling of the extracellular matrix or by secreting cytokines. CAFs are a complex and abundant cell type within the tumour microenvironment.<br> Fibroblasts are the most abundant cells in the tumor microenvironment, also called tumor-associated fibroblasts (TAFs). They are known to secrete a variety of soluble factors, such as metalloproteinases (MMPs), enzymes that are related to changes in the extracellular matrix, promoting tumor invasion.<br>
929-	CAIX	↑	Carbonic Anhydrase IX			<b>CAIX (Carbonic Anhydrase IX)</b> is a transmembrane enzyme that plays a crucial role in maintaining the pH balance in cells and their surroundings. In the context of cancer, CAIX has been found to be overexpressed in various types of tumors.<br> CAIX is overexpressed in cancer cells compared to normal cells. This overexpression is thought to contribute to the increased ability of cancer cells to survive and grow in hypoxic environments.<br>
1000-	cal2	↓	calpain-2			<b>Calpain-2</b> is a calcium-dependent cysteine protease that plays important roles in a variety of cellular processes, including migration, adhesion, signal transduction, and apoptosis.<br> In many cancer types, Calpain-2 is found to be upregulated. Elevated levels of Calpain-2 have been associated with enhanced proteolytic activity, which can contribute to cancer progression by facilitating processes such as cell migration, invasion, and metastasis.<br> • The increased expression of Calpain-2 in cancer cells can promote the degradation of cytoskeletal and adhesion proteins, thereby aiding in tumor cell detachment and dissemination. This is particularly relevant during epithelial-to-mesenchymal transition (EMT) and remodeling of the extracellular matrix.<br> • Calpain-2 activity, which is regulated by intracellular Ca²⁺ levels and calpastatin (its endogenous inhibitor), may also influence signal transduction pathways that are critical for cell proliferation and survival. Alterations in these regulatory mechanisms in a tumor setting can amplify Calpain-2’s impact.<br> <br> Calpain-2 is commonly upregulated in many cancer types, and this increased expression is thought to promote tumor progression by enhancing cellular invasiveness, migration, and survival through its proteolytic actions.<br>
756-	Calcium	↑	Calcium mineralization			<b>Calcium mineralization</b> refers to the process by which calcium ions are deposited in tissues, leading to the hardening of structures such as bones and teeth. <br> The expression levels of calcium-related proteins can correlate with cancer prognosis. For example, high levels of certain calcium-binding proteins may be associated with poor outcomes in specific cancers.<br> Some tumors may exhibit calcification, which can be detected through imaging techniques. The presence of calcifications can sometimes indicate a more aggressive tumor type or specific cancer subtypes.<br>
1142-	CaMKII	↑	Calcium/Calmodulin-dependent Protein Kinase II			<b>CaMKII</b>, short for Calcium/Calmodulin-dependent Protein Kinase II, is not a single protein but rather a family of related enzymes composed of several isoforms. <br> Breakdown:<br> CaMKII Isoforms:4 genes encoding the major isoforms: α(alpha), β(beta), γ(gamma), and δ(delta). CaMKIIα and CaMKIIβ are abundant in neuronal tissue, while CaMKIIδ is more prevalent in the heart and other non-neuronal tissues.<br> <br> -Overexpression or hyperactivation of CaMKII has been linked in some studies to enhanced cell cycle progression and resistance to apoptosis, both of which are features of more aggressive tumors.<br> -In some cancers, upregulation or increased activity of CaMKII has been associated with poor clinical outcomes, including lower overall survival or higher recurrence rates.<br>
761-	cAMP	⇅	cyclic adenosine monophosphate			<b>cAMP (cyclic adenosine monophosphate)</b> is a secondary messenger molecule that plays a crucial role in various cellular processes, including cell signaling, metabolism, and gene expression. In the context of cancer, cAMP has been found to have both tumor-promoting and tumor-suppressing effects.<br>
783-	carcinogenesis	↑	carcinogenesis			<b>Carcinogenesis</b> is the process by which normal cells are transformed into cancer cells.<br>
39-	CARD11	↑	caspase recruitment domain family, member 11	CGL-Driver Genes	Oncogene	<b>In normal B cells,</b> antigen receptor-induced NF-kappaB activation requires CARD11, a cytoplasmic scaffolding protein.<br> CARD11 is a bona fide oncogenein DLBCL, providing a genetic rationale for the development of pharmacological inhibitors of the CARD11 pathway for DLBCL therapy.<br> Aberrant expression of CARD11 can promote cancer pathogenesis through changes to mTOR signaling and autophagy.<br>
1188-	cardioP	∅	cardioProtective			<b>CardioProtective</b> <br>
1108-	CardioT	↑	Cardiotoxicity			<b>Cardiotoxicity</b> in the context of cancer generally refers to the potential harmful effects that cancer therapies can have on the heart. This is an important consideration because many effective cancer treatments can also damage cardiac tissue, leading to short-term or long-term cardiovascular complications. <br> <br> Mechanisms of Cardiotoxicity in Cancer Therapy<br> -Chemotherapy Agents:<br>      Anthracyclines (e.g., doxorubicin, epirubicin):<br>      Alkylating Agents (e.g., cyclophosphamide):<br>      Antimetabolites (e.g., 5-fluorouracil, capecitabine):<br> -Targeted Therapies:<br>     HER2 inhibitors (e.g., trastuzumab):<br>     Tyrosine Kinase Inhibitors (e.g., sunitinib, imatinib):<br> -Radiation Therapy:<br>     Thoracic irradiation:<br> <br> Natural Products that may reduce Cardiotoxicity:<br> -Resveratrol<br> -Curcumin<br> -EGCG<br> -Quercetin<br> -Garlic Extract (Allicin)<br> -Omega-3 Fatty Acids: Fish oil (EPA and DHA), flaxseeds, chia seeds, walnuts.<br> <br> <br> Natural products like resveratrol, curcumin, EGCG, quercetin, garlic extract, and omega-3 fatty acids show potential in reducing cardiotoxicity by targeting oxidative stress, inflammation, and apoptotic pathways.<br>
941-	CarnA	↑	Carnitine Acyltransferase			<b>(Carnitine Acyltransferase)</b> is an enzyme that plays a crucial role in the metabolism of fatty acids. In the context of cancer, CAT expression has been studied in various types of tumors.<br> (Carnitine Acyltransferase) is typically upregulated in various types of cancer. Studies have shown that CAT expression is increased in many types of cancer, including breast, colorectal, prostate, lung, liver, pancreatic, and glioblastoma, among others.<br> High expression is linked to poor prognosis.<br> <br> Carnitine acyltransferases” is an umbrella term covering a family of enzymes involved in the transport and metabolism of acyl‐groups (typically long‐chain fatty acids) by conjugation with carnitine. The key members include:<br> CPT1 (Carnitine Palmitoyltransferase 1) -frequently upregulated in cancer<br> CPT2 (Carnitine Palmitoyltransferase 2)<br> CACT (Carnitine Acylcarnitine Translocase)<br> CrAT (Carnitine Acetyltransferase<br> <br> Many studies have shown that enzymes facilitating fatty acid oxidation (especially CPT1A) can be upregulated in cancers that rely on fatty acid oxidation to boost their energy production and support biosynthesis. This upregulation is an adaptation to increased energy demands and altered nutrient availability.<br>
539-	Cartilage	↓	Cartilage			<b>Cartilage</b> is a flexible connective tissue found in multiple areas of the body, including joints, the ear and nose, and intervertebral discs.<br> The most common type of arthritis, osteoarthritis involves wear-and-tear damage to a joint's cartilage.<br> Chondrosarcoma is a rare type of bone cancer that develops in cartilage cells.<br> <b>Cartilage Degradation:</b> Cancer can lead to the degradation of cartilage, particularly in joint-related cancers. This degradation can result in pain and loss of function, impacting the patient's quality of life.<br> <b>Biomarkers:</b> Specific proteins and genes associated with cartilage metabolism (e.g., collagen types, aggrecan, and matrix metalloproteinases) can serve as biomarkers for cancer diagnosis and prognosis. Their expression levels may indicate the presence of malignancy or the aggressiveness of a tumor.<br>
443-	Casp	?	caspase			<b>The caspase family</b> of proteases are essential to initiate and execute apoptotic cell death. Targeting caspase pathways by gene therapy or endogenous inhibitors represents a promising therapeutic strategy for cancer.<br> Caspases are divided into two groups: the initiator caspases (caspase-2, -8, -9 and -10), which are the first to be activated in response to a signal, and the executioner caspases (caspase-3, -6, and -7) that carry out the demolition phase of apoptosis.<br> Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.<br>
41-	Casp1	↑	Caspase-1			<b>Also known as ICE </b>(Interleukin-1 beta Convertase).<br> Caspases are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.<br> Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer.<br> Caspase-1:<br> Role: Involved in inflammation and pyroptosis.<br> Cancers: Elevated in certain cancers, including colorectal cancer and pancreatic cancer.<br> Prognosis: High levels may be associated with a more aggressive tumor phenotype.<br>
445-	Casp10	↓	cysteine-aspartic protease 10			<b>Caspase-10</b> is a member of the caspase family of cysteine proteases, which play essential roles in programmed cell death (apoptosis) and inflammation.<br> Caspase-10 is crucial for the induction of apoptosis in response to various signals. In many cancers, the apoptotic pathways are dysregulated, allowing cancer cells to evade programmed cell death. Loss of caspase-10 function or expression can contribute to this evasion, promoting tumor survival and growth.<br> Caspase-10 may act as a tumor suppressor. Its expression can be downregulated in various cancers, including breast, colorectal, and prostate cancers.<br> Caspase-10 is frequently downregulated in various cancers, which may contribute to the evasion of apoptosis and tumor progression.<br>
595-	Casp12	?	Caspase-12			<b>Caspase-12:</b> a member of the caspase family, a group of cysteine proteases that play a crucial role in programmed cell death, also known as apoptosis. Caspase-12 is specifically involved in the endoplasmic reticulum (ER) stress-induced apoptosis pathway.<br> On one hand, caspase-12 can act as a tumor suppressor by promoting apoptosis in response to ER stress, which can occur in cancer cells due to their high metabolic rate and increased demand for protein synthesis.<br> <br> On the other hand, some studies have suggested that caspase-12 can also contribute to cancer progression and resistance to chemotherapy. For example, caspase-12 can be inactivated in certain types of cancer, such as breast and lung cancer, which can lead to reduced apoptosis and increased tumor growth.<br> Role of Caspase-12:<br> Function: Caspase-12 is involved in the apoptotic pathway triggered by ER stress. It can activate downstream effector caspases, leading to apoptosis. It also plays a role in the inflammatory response by processing pro-inflammatory cytokines.<br> Location: Unlike many other caspases, caspase-12 is primarily localized in the cytosol and the ER.<br>
1063-	Casp2	↓	caspase-2			<b>Caspase‑2</b> is an initiator caspase that, unlike other apoptotic caspases, can also function in non‐apoptotic pathways including DNA damage responses.<br> Its unique position in guarding genomic integrity has led to studies examining its tumor-suppressive potential.<br> <br> Caspase‑2 plays complex roles in cancer biology. Generally, decreased expression or altered isoform distribution of caspase‑2 has been associated with impaired apoptotic responses, genomic instability, and poorer prognosis in several cancer types.<br>
42-	Casp3	↓	CPP32, Cysteinyl aspartate specific proteinase-3			<b>Also known as CP32.</b><br> Cysteinyl aspartate specific proteinase-3 (Caspase-3) is a common key protein in the apoptosis and pyroptosis pathways, and when activated, the expression level of tumor suppressor gene Gasdermin E (GSDME) determines the mechanism of tumor cell death. <br> As a key protein of apoptosis, caspase-3 can also cleave GSDME and induce pyroptosis. Loss of caspase activity is an important cause of tumor progression. <br> Many anticancer strategies rely on the promotion of apoptosis in cancer cells as a means to shrink tumors. Crucial for apoptotic function are executioner caspases, most notably caspase-3, that proteolyze a variety of proteins, inducing cell death. Paradoxically, overexpression of procaspase-3 (PC-3), the low-activity zymogen precursor to caspase-3, has been reported in a variety of cancer types. Until recently, this counterintuitive overexpression of a pro-apoptotic protein in cancer has been puzzling. Recent studies suggest subapoptotic caspase-3 activity may promote oncogenic transformation, a possible explanation for the enigmatic overexpression of PC-3. Herein, the overexpression of PC-3 in cancer and its mechanistic basis is reviewed; collectively, the data suggest the potential for exploitation of PC-3 overexpression with PC-3 activators as a targeted anticancer strategy.<br> Caspase 3 is the main effector caspase and has a key role in apoptosis. In many types of cancer, including breast, lung, and colon cancer, caspase-3 expression is reduced or absent.<br> On the other hand, some studies have shown that high levels of caspase-3 expression can be associated with a better prognosis in certain types of cancer, such as breast cancer. This suggests that caspase-3 may play a role in the elimination of cancer cells, and that therapies aimed at activating caspase-3 may be effective in treating certain types of cancer.<br> Procaspase-3 is a apoptotic marker protein.<br> Prognostic significance:<br> • High Cas3 expression: Associated with good prognosis and increased sensitivity to chemotherapy in breast, gastric, lung, and pancreatic cancers.<br> • Low Cas3 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.<br>
620-	Casp6	↑	Caspase-6			<b>A member of the caspase family,</b> a group of cysteine proteases that play a crucial role in programmed cell death, also known as apoptosis. <br> Caspase-6 has been found to be overexpressed in various types of cancer, including breast, lung, and colon cancer. However, its expression levels and activity can vary depending on the type of cancer and the stage of disease progression.<br> Inhibitors of caspase-6 have been shown to have anti-tumor effects in preclinical studies, while activators of caspase-6 have been found to induce apoptosis in cancer cells.<br>
43-	Casp7	?	Caspase-7			<b>Members of the caspase</b> family of proteases play essential roles in the initiation and execution of apoptosis. These caspases are divided into two groups: the initiator caspases (caspase-2, −8, −9 and −10), which are the first to be activated in response to a signal, and the executioner caspases (caspase-3, −6, and −7) that carry out the demolition phase of apoptosis. Downregulation of caspase-3 is an effective apoptosis-evading mechanism frequently observed in cancer cells in association with acquired chemoresistance to apoptosis-inducing anticancer drugs. Indeed, re-expression of caspase-3 often restores sensitivity to apoptosis.<br> Caspase-7:<br> Role: Executioner caspase similar to caspase-3.<br> Cancers: Expression levels can vary; often studied in breast and prostate cancers.<br> Prognosis: Its prognostic value is less clear and may depend on the cancer type.<br>
44-	Casp8	?	CASP8, caspase 8, apoptosis-related cysteine peptidase	CGL-Driver Genes	TSG	<b>Caspase-8</b> is a unique member of caspases with a dual role in cell death and survival. Caspase-8 expression is often lost in some tumors, but increased in others, indicating a potential pro-survival function in cancer. <br> Caspase-8 (Casp8) acts as an initiator in cell apoptosis signaling. However, the role of Casp8 in tuning the tumor immune microenvironment remains controversial due to the complicated crosstalk between immune-tolerogenic apoptotic cell death and immunogenic cell death cascades.<br>
45-	Casp9	↓	Caspase-9			<b>Caspase-9</b> is the apoptotic initiator protease of the intrinsic or mitochondrial apoptotic pathway, which is activated at multi-protein activation platforms. <br> Caspases are divided into two groups: the initiator caspases (caspase-2, -8, -9 and -10), which are the first to be activated in response to a signal, and the executioner caspases (caspase-3, -6, and -7) that carry out the demolition phase of apoptosis.<br> Caspase-9:<br> Role: Initiator caspase in the intrinsic apoptotic pathway.<br> Cancers: Frequently studied in leukemia and solid tumors.<br> Prognosis: Reduced expression is often linked to chemoresistance and poor prognosis.<br>
46-	Catalase	?	Catalase			<b>Caspases</b> are a cysteine protease that speed up a chemical reaction via pointing their target substrates following an aspartic acid residue.1 They are grouped into apoptotic (caspase-2, 3, 6, 7, 8, 9 and 10) and inflammatory (caspase-1, 4, 5, 11 and 12) mediated caspases.<br> Caspase-1 may have both tumorigenic or antitumorigenic effects on cancer development and progression, but it depends on the type of inflammasome, methodology, and cancer.<br> Catalase is an enzyme found in nearly all living cells exposed to oxygen. Its primary role is to protect cells from oxidative damage by catalyzing the conversion of hydrogen peroxide (H₂O₂), a potentially damaging byproduct of metabolism, into water (H₂O) and oxygen (O₂). This detoxification process is crucial because excess H₂O₂ can lead to the formation of reactive oxygen species (ROS) that damage proteins, lipids, and DNA.<br> <br> Catalase and Cancer<br> Oxidative Stress and Cancer:<br> Cancer cells often experience increased levels of oxidative stress due to rapid proliferation and metabolic changes. This stress can lead to DNA damage, promoting tumorigenesis.<br> Catalase helps mitigate oxidative stress, and its expression can influence the survival and proliferation of cancer cells.<br> Expression Levels in Different Cancers:<br> Overexpression: In some cancers, such as breast cancer and certain types of leukemia, catalase may be overexpressed. This overexpression can help cancer cells survive in oxidative environments, potentially leading to more aggressive tumor behavior.<br> Downregulation: Conversely, in other cancers, such as colorectal cancer, reduced catalase expression has been observed. This downregulation can lead to increased oxidative stress, contributing to tumor progression and metastasis.<br> Prognostic Implications:<br> Survival Rates: Studies have shown that high levels of catalase expression can be associated with poor prognosis in certain cancers, as it may enable cancer cells to resist apoptosis (programmed cell death) induced by oxidative stress.<br> <br> Some types of cancer cells have been reported to exhibit lower catalase activity, possibly increasing their vulnerability to oxidative damage under certain conditions. This vulnerability has even been exploited in some therapeutic strategies (for example, approaches that generate excess H₂O₂ or other ROS specifically targeting cancer cells have been researched).<br>
922-	Cav1	?	Caveolin-1		protein	<b>Caveolin-1 (Cav-1)</b> is a protein that plays a crucial role in the structure and function of caveolae, which are small, flask-shaped invaginations of the plasma membrane found in many cell types. Cav-1 has been implicated in various cellular processes, including cell signaling, cholesterol transport, and apoptosis.<br> <br> In the context of cancer, Cav-1 has been found to have both tumor-suppressive and tumor-promoting roles, depending on the type of cancer and the stage of disease progression.<br>
47-	CBL	?	Casitas B-lineage Lymphoma	CGL-Driver Genes	Oncogene	<b>Cbl (named after Casitas B-lineage Lymphoma)</b> is a mammalian gene family. CBL gene, a part of the Cbl family, encodes the protein CBL which is an E3 ubiquitin-protein ligase involved in cell signalling and protein ubiquitination. Mutations to this gene have been implicated in a number of human cancers, particularly acute myeloid leukaemia.<br> There are three mammalian Cbl proteins encoded by separate genes: Cbl (a.k.a., c-Cbl, CBL2, RNF55), Cbl-b (a.k.a., RNF56), and Cbl-c (a.k.a., Cbl-3, Cbl-SL, RNF57;)<br> Cbl functions as a tumor suppressor by E3-dependent ubiquitination and downregulation of activated RTKs. Cbl can function also as an oncogene by mediating adaptor function-dependent activation of downstream signaling to the PI3K/AKT pathway.<br> CAS-BR-M MURINE ECOTROPIC RETROVIRAL TRANSFORMING SEQUENCE C; CBLC<br>
501-	CBP	↑	CREB-binding protein			<b>CBP</b> is a transcriptional coactivator that plays a crucial role in regulating gene expression, and it has been implicated in various cellular processes, including cell growth, differentiation, and apoptosis.<br> CBP is of interest because it can influence the activity of oncogenes and tumor suppressor genes. CBP can act as an oncogene in certain contexts. Its ability to enhance the transcription of genes that promote cell proliferation and survival can contribute to tumorigenesis. Overexpression of CBP has been observed in various cancers, including breast, colon, and prostate cancers.<br> CBP may also function as a tumor suppressor. For instance, mutations or loss of CBP expression can lead to the activation of oncogenic pathways. This dual role can depend on the specific cellular context and the presence of other signaling molecules.<br> CBP interacts with numerous transcription factors, including p53, which is a well-known tumor suppressor. The interaction between CBP and p53 is crucial for p53's role in regulating the cell cycle and apoptosis. Dysregulation of this interaction can lead to cancer development.<br> Overexpressed: breast,CRC, prostate, lung, HCC, ovrian, bladder, pancreatic, head and neck, AML.<br>
55-	CC(CDKs/cyclins)	↑	Cell cycle (CDKs/cyclins)	HalifaxProj(attenuate) TCGA		<b>Cyclins and cyclin-dependent kinases (CDKs)</b> are key regulators of the cell cycle, and their dysregulation is a common feature in many cancers. <br> The cell cycle consists of several phases:<br> G1 Phase (Gap 1): The cell grows and prepares for DNA synthesis.<br> S Phase (Synthesis): DNA is replicated.<br> G2 Phase (Gap 2): The cell prepares for mitosis.<br> M Phase (Mitosis): The cell divides into two daughter cells.<br> <br> Open menu<br> Cdh1 and E-cadherin are they the same thing<br> <br> Cdh1 and E-cadherin refer to the same protein. Cdh1 is the gene that encodes E-cadherin, which is a type of cadherin, a family of proteins involved in cell-cell adhesion. E-cadherin plays a crucial role in maintaining the structure and integrity of tissues by facilitating adhesion between epithelial cells. It is particularly important in the context of development and in the maintenance of epithelial tissue architecture. In summary, Cdh1 is the gene name, while E-cadherin is the protein product of that gene.<br> <br> CDK1/2/5/9 role in cancer<br> <br> Cyclin-dependent kinases (CDKs) are a family of protein kinases that play essential roles in regulating the cell cycle, transcription, and other cellular processes. CDK1, CDK2, CDK5, and CDK9 have been implicated in cancer through various mechanisms:<br> <br> <b>CDK1:</b><br> Role: Primarily involved in the regulation of the cell cycle, particularly the transition from G2 phase to mitosis.<br> Cancer Implication: Overexpression or hyperactivation of CDK1 can lead to uncontrolled cell proliferation and is often associated with various cancers, including breast, colorectal, and lung cancers. CDK1 inhibitors are being explored as potential cancer therapies.<br> <b>CDK2:</b><br> Role: Functions mainly in the G1 to S phase transition of the cell cycle, working closely with cyclins D and E.<br> Cancer Implication: CDK2 is often overexpressed in cancer cells, contributing to tumorigenesis by promoting cell cycle progression. Inhibition of CDK2 has been studied as a therapeutic strategy in cancers such as ovarian and breast cancer.<br> <b>CDK5:</b><br> Role: Unlike other CDKs, CDK5 is primarily involved in neuronal function and is activated by p35 and p39. It plays roles in neuronal development and synaptic function. Cancer Implication: CDK5 has been implicated in certain cancers, particularly in the context of neurodegenerative diseases and brain tumors. Its role in cancer is complex, as it can promote or inhibit tumor growth depending on the context and the specific cancer type.<br> <b>CDK9:</b><br> Role: Part of the positive transcription elongation factor b (P-TEFb) complex, CDK9 is involved in regulating transcription by phosphorylating the C-terminal domain of RNA polymerase II. Cancer Implication: CDK9 is often overexpressed in various cancers, leading to increased transcription of genes that promote cell survival and proliferation. Inhibitors of CDK9 are being investigated as potential cancer therapies, particularly in hematological malignancies. In summary, CDK1, CDK2, CDK5, and CDK9 each play distinct roles in cell cycle regulation and transcription, and their dysregulation is associated with various cancer types. Targeting these kinases with specific inhibitors is an area of active research in cancer therapy.<br> <br> <br> CDK4 and CDK6 are cyclin-dependent kinases that play crucial roles in regulating the cell cycle, particularly the transition from the G1 phase to the S phase. Their activity is tightly regulated by cyclins, specifically cyclin D, and they are essential for cell proliferation. Here’s how CDK4 and CDK6 are implicated in cancer:<br> <br> <b>Role in Cell Cycle Regulation</b><br> CDK4/6 Function: CDK4 and CDK6, when activated by cyclin D, phosphorylate the retinoblastoma protein (Rb). This phosphorylation leads to the release of E2F transcription factors, which promote the expression of genes necessary for DNA synthesis and progression into the S phase of the cell cycle. <b>Implications in Cancer</b><br> Overexpression and Dysregulation: In many cancers, CDK4 and CDK6 are often overexpressed or hyperactivated, leading to uncontrolled cell proliferation. This dysregulation can result from various factors, including mutations in cyclins, loss of tumor suppressor genes (like Rb), or amplification of the CDK4/6 genes themselves.<br> <b>Breast Cancer:</b> CDK4/6 is particularly well-studied in hormone receptor-positive breast cancer. In these cancers, the overactivity of CDK4/6 contributes to tumor growth and progression. Other Cancers: CDK4/6 has also been implicated in other cancers, including melanoma, lung cancer, and certain hematological malignancies.<br> <b>Therapeutic Targeting</b><br> CDK4/6 Inhibitors: The discovery of the role of CDK4 and CDK6 in cancer has led to the development of specific inhibitors, such as palbociclib, ribociclib, and abemaciclib. These drugs have shown efficacy in treating hormone receptor-positive breast cancer, often in combination with endocrine therapies (like aromatase inhibitors or tamoxifen).<br> Mechanism of Action: By inhibiting CDK4/6, these drugs prevent the phosphorylation of Rb, thereby blocking the cell cycle progression from G1 to S phase, leading to reduced cell proliferation and increased apoptosis in cancer cells.<br> <b>Conclusion</b><br> CDK4 and CDK6 are critical regulators of the cell cycle, and their dysregulation is a common feature in various cancers. Targeting these kinases with specific inhibitors has become a promising therapeutic strategy, particularly in hormone receptor-positive breast cancer, and ongoing research continues to explore their role in other malignancies.<br> <br> Cell cycle (CDKs/cyclins) and cancer<br> <br> The cell cycle is a tightly regulated series of events that lead to cell division and replication. Cyclins and cyclin-dependent kinases (CDKs) are key regulators of the cell cycle, and their dysregulation is a common feature in many cancers. Here’s an overview of how CDKs and cyclins function in the cell cycle and their implications in cancer:<br> <br> <b>Cell Cycle Phases</b><br> The cell cycle consists of several phases:<br> <br> G1 Phase (Gap 1): The cell grows and prepares for DNA synthesis.<br> S Phase (Synthesis): DNA is replicated.<br> G2 Phase (Gap 2): The cell prepares for mitosis.<br> M Phase (Mitosis): The cell divides into two daughter cells.<br> <b>Role of CDKs and Cyclins</b><br> Cyclins: These are regulatory proteins whose levels fluctuate throughout the cell cycle. They activate CDKs by binding to them, forming cyclin-CDK complexes that drive the cell cycle forward. CDKs: These are serine/threonine kinases that, when activated by cyclins, phosphorylate target proteins to regulate various processes, including:<br> Progression through the cell cycle.<br> DNA replication.<br> Mitotic entry and exit.<br> <b>Key CDKs and Their Functions</b><br> CDK1: Regulates the transition from G2 to M phase.<br> CDK2: Involved in the G1 to S phase transition.<br> CDK4 and CDK6: Work with cyclin D to promote progression through the G1 phase.<br> CDK2: Also works with cyclin E to facilitate the G1/S transition.<br> FRO9: Involved in transcriptional regulation and elongation.<br> Overexpression: Many cancers exhibit overexpression of cyclins (e.g., cyclin D1) or CDKs (e.g., CDK4/6), leading to uncontrolled cell proliferation.<br>
56-	CC/Apoptosis	?	Cell Cycle / Apoptosis	CGL-CS		<b>Driver genes</b> that directly regulate the cell cycle or apoptosis, such as CDKN2A, MYC, and BCL2, are often mutated in cancers. Another gene whose mutations enhance cell survival is VHL, the product of which stimulates angiogenesis through the secretion of vascular endothelial growth factor. <br>
555-	CCDC150	↑	CCDC150, Coiled-coil domain-containing (CCDC) proteins			<b>Coiled-coil domain-containing (CCDC)</b> proteins constitute a class of homo-oligomeric or oligomeric sequence proteins containing two or more coiled-coil structural domains, crucial for the assembly and arrangement of the cytoskeleton.<br> CCDC150 is a prognostic marker in Kidney renal clear cell carcinoma, Pancreatic adenocarcinoma Cancer.<br> CCDC150, which exhibited abnormal expression in TNBC and responded to gradient RMF. CCDCs participate in the formation of backbone proteins and the polymerization of actin, which is pivotal in driving the epithelial–mesenchymal transition of tumor cells. Abnormal up-regulation of some CCDCs is found in tumors, and they are positively correlated with tumor metastasis. For instance, CCDC6 exhibits aberrantly high expression in thyroid cancer, and CCDC66 is significantly up-regulated in colorectal cancer to promote tumor invasion and metastasis. We found that the expression of CCDC150 in TNBC was significantly increased.<br>
1055-	CCL20	↑	Chemokine [C-C motif] ligand 20			<b>CCL20 (Chemokine [C-C motif] ligand 20),</b> also known as MIP-3α, plays a role in immune cell recruitment and inflammation. <br> <br> Upregulation in Tumors:<br> – Many studies have noted elevated levels of CCL20 in tumor tissues compared to adjacent normal tissues in various cancers such as colorectal, hepatocellular, breast, and pancreatic cancers.<br> – Increased CCL20 expression is often associated with an inflammatory tumor microenvironment that promotes tumor cell migration and invasion.<br> <br> Elevated CCL20 levels have been correlated with enhanced tumor invasiveness and metastasis in several cancer types, likely driven by its ability to modulate the local immune response and promote a pro-tumorigenic microenvironment.<br>
1067-	CD11b	↑	CD11b			<b>CD11b’s</b> (also known as integrin αM or ITGAM).<br> Markers CD14 and CD11b is one of the important characteristics of differentiation.<br> <br> High levels of CD11b are often noted in the tumor microenvironment.<br> A high density of CD11b⁺ cells in the tumor microenvironment has been associated with adverse prognosis. For example, an abundance of MDSCs (which are CD11b⁺) is linked to immunosuppression, tumor progression, and resistance to therapies. High levels of CD11b⁺ cell infiltration have been correlated with:<br> -Faster tumor progression.<br> -Increased metastasis.<br> -Reduced response to immunotherapies.<br>
677-	CD133	↑	prominin-1			<b>CD133</b>, also known as prominin-1, is a pentaspan transmembrane glycoprotein that is commonly used as a marker for stem cells, particularly in the context of cancer research. It is a cell surface protein that is expressed on the surface of many types of stem cells, including embryonic stem cells, hematopoietic stem cells, and cancer stem cells.<br> <br> CD133 is often used as a marker to identify and isolate cancer stem cells, which are thought to be responsible for the initiation and progression of cancer. <br> <br> High levels of CD133 expression have been associated with poor prognosis and reduced overall survival in various types of cancer.<br>
1068-	CD14	↑	CD14			<b>CD14</b> is a co-receptor that recognizes several ligands, including bacterial lipopolysaccharide (LPS) and other pathogen-associated molecular patterns (PAMPs). It plays a pivotal role in innate immunity by identifying danger signals.<br> CD14 works in close cooperation with Toll-like receptors (TLRs), especially TLR4.<br> <br> CD14 is highly expressed in myeloid cells within the tumor microenvironment, such as tumor-associated macrophages (TAMs) and certain dendritic cell subsets. <br> A high prevalence of CD14⁺ cells within the tumor microenvironment is associated with chronic inflammation, which in turn can contribute to tumor progression, angiogenesis, and eventual metastasis.<br>
655-	CD24-	?	CD24-			<b>CD24</b> is a cell surface protein that plays a role in cell adhesion and signaling. In the context of cancer, CD24 has been found to be overexpressed in many types of cancer, including breast, ovarian, and pancreatic cancer.<br> CD24− refers to cells that do not express CD24.<br> CD24− cells in cancer are often more resistant to chemotherapy and radiation therapy, and may be more likely to metastasize (spread) to other parts of the body. <br> CD24− cells have been found to be more likely to be cancer stem cells, which are thought to be responsible for the initiation and progression of cancer.<br>
712-	CD25+	↑	IL-2Rα interleukin-2 receptor alpha			<b>CD25,</b> also known as interleukin-2 receptor alpha (IL-2Rα) chain, is a protein that plays a crucial role in the immune system. Primarily expressed on the surface of activated T cells, regulatory T cells (Tregs), and some types of cancer cells.<br> <br> CD25+ cells have been found to be associated with various types of tumors.<br>
295-	CD31	↑	platelet endothelial cell adhesion molecule-1 (PECAM-1)		marker	<b>CD31</b>, also known as platelet endothelial cell adhesion molecule-1 (PECAM-1), is a transmembrane receptor that plays a crucial role in various cellular processes, including cell adhesion, migration, and signaling.<br> High CD31 expression has been linked to poor prognosis and increased metastasis. (except Leukemia and brain cancers).<br> CD31 is a marker that is commonly used to identify microvessels in tissue sections.<br>
629-	CD34	↑	CD34 transmembrane phosphoglycoprotein protein			<b>CD34</b> is a transmembrane phosphoglycoprotein protein that is expressed on the surface of certain cells, including hematopoietic stem cells, endothelial progenitor cells, and some cancer cells. In the context of cancer, CD34 has been studied as a potential biomarker and therapeutic target.<br> CD34 has been shown to be expressed on cancer stem cells in various types of cancer, including leukemia, breast cancer, and lung cancer.<br>
856-	CD38	↑	CD38 protein		protein	<b>CD38</b> is a type of protein found on the surface of many cells, including immune cells and some cancer cells. It plays a crucial role in cell signaling, cell adhesion, and the regulation of calcium levels within cells.<br> CD38 has been found to be overexpressed in various types of tumors, including multiple myeloma, lymphoma, and leukemia. This overexpression can contribute to the development and progression of cancer by promoting cell proliferation, survival, and metastasis.<br>
544-	CD4+	?	CD4+ T Cells			<b>CD4+ T cells</b> are T lymphocytes that express T cell receptors (TCRs).<br> Majority of cancer immunotherapies focus on harnessing the anti-tumour CD8+ cytotoxic T cell response, the potential role of CD4+ ‘helper’ T cells has largely remained in the background. multifaceted role of CD4+ T cells in the anti-tumour immune response.<br> CD4+ T cells play a critical role in developing and sustaining effective anti-tumour immunity, even in cancer immunotherapies specifically designed to activate a CD8+ CTL response.<br>
48-	CD44	↑	CD44			<b>CD44</b> represents a common biomarker of cancer stem cells, and promotes epithelial-mesenchymal transition. CD44 is a well-known marker of CSCs and plays important roles in tumor initiation and development.<br>
1030-	CD69	?	CD69			<b>CD69</b> is traditionally known as an early activation marker on T cells, natural killer (NK) cells, and other leukocytes.<br> Elevated CD69 expression on tumor-infiltrating lymphocytes (TILs) may reflect an ongoing anti-tumor immune response.<br> <br> CD69 is an early lymphocyte activation marker that plays multifaceted roles in the tumor microenvironment, influencing cell retention, activation, and antitumor immune responses. In various cancers—including melanoma, breast cancer, NSCLC, HNSCC, and hematologic malignancies—the expression of CD69 on tumor-infiltrating immune cells often correlates with an active antitumor response and, in many cases, improved patient prognosis.<br>
344-	CD8+	?	CD8+ T cell		T cell	<b>CD8+ T cells</b> are "end effectors" of cancer immunity.<br> Cytotoxic T cells expressing cell-surface CD8 are the most powerful effectors in the anticancer immune response and form the backbone of current successful cancer immunotherapies.<br> CD8+ T cells, also known as cytotoxic T lymphocytes (CTLs), play a crucial role in the immune response against cancer. They are responsible for identifying and killing cancer cells that present abnormal antigens, which can arise from mutations or viral infections.<br>
499-	CDC16	?	Cell Division Cycle 16			<b>CDC16 (Cell Division Cycle 16)</b> is a protein that plays a crucial role in the regulation of the cell cycle, particularly during the process of mitosis. It is part of the anaphase-promoting complex/cyclosome (APC/C), which is essential for the progression of the cell cycle and the proper segregation of chromosomes during cell division.<br>
439-	cDC2	?	type 2 conventional dendritic cell			<b>Play an important role</b> in antitumor immunity by promoting cytotoxic T-cell responses and helper T-cell differentiation. <br> Dendritic cells (DCs) consist of three major subsets termed plasmacytoid (pDCs), type-1 (cDC1s), and type-2 (cDC2s) conventional (or classical) DCs.<br>
526-	CDC25	↑	Cell Division Cycle 25			<b>CDC25 (Cell Division Cycle 25)</b> is a family of dual-specificity phosphatases that play a crucial role in regulating the cell cycle. There are three main isoforms of CDC25: CDC25A, CDC25B, and CDC25C. These proteins are involved in the activation of cyclin-dependent kinases (CDKs) by dephosphorylating them, which is essential for the progression of the cell cycle from G2 phase to mitosis.<br> CDC25 proteins, particularly CDC25A, are often found to be overexpressed in various types of cancer. This overexpression can lead to uncontrolled cell proliferation, as the normal regulatory mechanisms of the cell cycle are disrupted.<br> High levels of CDC25 have been associated with advanced stages of cancer and poor prognosis in several malignancies, including breast, colorectal, and prostate cancers.<br> CDC25 interacts with various oncogenes and tumor suppressor proteins, such as p53. The loss of p53 function, which is common in many cancers, can lead to increased CDC25 activity, further promoting tumorigenesis.<br> CDC25A overexpressed: breast, CRC, lung, prostate.<br> CDC25B: breast, ovarian, lung.<br> CDC25C: liver,breast, prostate.<br>
880-	Cdc42	↑	Cdc42cdc2			<b>Cdc42</b> is a small GTPase that plays a crucial role in various cellular processes, including cell growth, migration, and survival.<br> High Cdc2 expression has been associated with poor prognosis and reduced overall survival in cancer patients.<br> Low Cdc2 expression has been associated with good prognosis and improved overall survival in cancer patients.<br>
498-	CDC7	↑	Cell Division Cycle 7			<b>CDC7 (Cell Division Cycle 7)</b> is a serine/threonine kinase that plays a crucial role in the regulation of the cell cycle, particularly in the initiation of DNA replication. It is involved in the phosphorylation of various substrates that are essential for the progression of the cell cycle is often found to be overexpressed in various types of cancer, including breast, colorectal, and prostate cancers.<br>
49-	CDC73	?	cell division cycle 73, Paf1/RNA polymerase II complex component, homolog (S. cerevisiae)	CGL-Driver Genes	TSG	<b>The role of human cell division cycle 73 (CDC73)</b> in human cancers has sparked controversy. up regulation of CDC73 in both oesophageal cancer cell lines.<br> Expression of CDC73 is also negatively associated with the progression of breast cancer patients.<br> Although tumor suppressor CDC73 has been less studied in OSCC, its low expression in other cancers and its anti-cancer effect have been widely confirmed.<br>
50-	CDH1	↓	cadherin 1, type 1, E-cadherin (epithelial)	CGL-Driver Genes	TSG	<b>Cdh1</b> is the gene name, while E-cadherin is the protein product of that gene.<br> Cdh1 is the gene that encodes E-cadherin, which is a type of cadherin, a family of proteins involved in cell-cell adhesion. E-cadherin plays a crucial role in maintaining the structure and integrity of tissues by facilitating adhesion between epithelial cells. It is particularly important in the context of development and in the maintenance of epithelial tissue architecture. <br> Germline mutation in CDH1 (E-cadherin) tumor suppressor gene is associated with hereditary diffuse gastric cancer (HDGC) and lobular breast cancers (LBC).<br> In general, reduced or lost expression of E-cadherin (CDH1) is often associated with more aggressive tumor behavior, increased invasiveness, and poorer prognosis across various cancer types.<br>
382-	CDK1	↑	Cyclin-dependent kinase 1			<b>CDK1, (Cyclin-dependent kinase 1)</b> same as p34 (cdc2) kinase activity<br> Cell cycle control to gene expression regulation and apoptosis, CDK1 is intimately involved in many cellular events that are vital for cell survival.<br> CDK1 is a significant biomarker in various cancers, with its overexpression often correlating with aggressive tumor characteristics and poor prognosis. Targeting CDK1 may offer therapeutic potential, especially in cancers where its expression is linked to unfavorable outcomes.<br>
51-	CDK1/2/5/9	↑	Cyclin-dependent kinases (CDKs)	HalifaxProj(inhibit)		<b>Cyclin-dependent kinases (CDKs)</b> are a family of protein kinases that play essential roles in regulating the cell cycle, transcription, and other cellular processes. CDK1, CDK2, CDK5, and CDK9 have been implicated in cancer through various mechanisms:<br> CDK1: regulation of the cell cycle. Overexpressed in various cancers.<br> CDK2: Functions mainly in the G1 to S phase transition of the cell cycle, working closely with cyclins D and E. Often overexpressed in cancers.<br> CDK5: primarily involved in neuronal function and is activated by p35 and p39. can promote or inhibit tumor growth depending on the context and the specific cancer type.<br> CDK9: regulating transcription by phosphorylating the C-terminal domain of RNA polymerase II. Often overrepresented in cancers.<br> Targeting these kinases with specific inhibitors is an area of active research in cancer therapy.<br>
467-	CDK2	↑	Cyclin-dependent kinase 2			<b>(CDK2)</b> complex is significantly over-activated in many cancers.<br> CDK2 interacts with and phosphorylates proteins in pathways such as DNA damage, intracellular transport, protein degradation, signal transduction, DNA and RNA metabolism and translation.<br>
894-	CDK4	↑	Cyclin-dependent kinase 4			<b>Cyclin-dependent kinase 4 (CDK4)</b> is a key regulator of the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression and activity are often altered in various cancers, contributing to tumorigenesis. <br> CDK4 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker.<br>
52-	CDK4/6	↑	CDK4/6	HalifaxProj(inhibit)		<b>CDK4 and CDK6</b> are critical regulators of the cell cycle, and their dysregulation is a common feature in various cancers. Targeting these kinases with specific inhibitors has become a promising therapeutic strategy, particularly in hormone receptor-positive breast cancer, and ongoing research continues to explore their role in other malignancies.<br> In many cancers, CDK4 and CDK6 are often overexpressed or hyperactivated, leading to uncontrolled cell proliferation.<br>
895-	CDK6	↑	Cyclin-dependent kinase 6			<b>Cyclin-dependent kinase 6 (CDK6)</b> is another important regulator of the cell cycle, particularly involved in the transition from the G1 phase to the S phase. <br> CDK6 is frequently overexpressed in various cancers, and its expression levels can serve as a prognostic marker. Targeting CDK6 with specific inhibitors, such as palbociclib (which also targets CDK4), has shown promise in clinical settings, particularly in hormone receptor-positive breast cancer. <br>
1036-	CDK8	↑	cyclin‐dependent kinase 8			<b>CDK8</b> is a member of the cyclin-dependent kinase family and is an integral component of the mediator complex, a multi-protein assembly that regulates transcription by RNA polymerase II. Unlike cell cycle CDKs, CDK8 primarily modulates transcriptional programs by phosphorylating transcription factors and other components of the transcription machinery. Its activity impacts various signaling pathways, including Wnt/β-catenin, Notch, and TGF-β, which are crucial for cell proliferation, differentiation, and survival.<br> <br> Overexpression or hyperactivation of CDK8 has been reported in various cancers, including colorectal cancer, melanoma, breast cancer, and others. Such dysregulation can contribute to abnormal transcriptional programs that favor oncogenesis.<br> Elevated levels or increased activity of CDK8 can enhance oncogenic signaling pathways. For instance, its role in potentiating the Wnt/β-catenin pathway has been associated with tumor growth and progression in colorectal cancers.<br> High CDK8 expression or activity has frequently been linked to more aggressive tumor phenotypes. In several studies, increased CDK8 has correlated with advanced disease stages and features such as enhanced metastatic potential, increased cell proliferation, and resistance to certain therapies.<br>
496-	CDKN1C	↓	cyclin-dependent kinase (CDK) inhibitors of the Cip/Kip family			<b>CDKN1C(p57 KIP2)</b><br> CDKN1C, also known as p57^KIP2, is a cyclin-dependent kinase inhibitor that plays a role in regulating the cell cycle. <br> Decreased expression of CDKN1C is often associated with more aggressive tumor behavior, increased invasiveness, and poorer prognosis across various cancer types.<br>
53-	CDKN2A	↓	cyclin-dependent kinase inhibitor 2A (melanoma, p16, inhibits CDK4)	CGL-Driver Genes	TSG	<b>CDKN2A</b> is a vital tumor suppressor gene that plays a key role in regulating the cell cycle and maintaining genomic stability.<br> CDKN2A (Cyclin-Dependent Kinase Inhibitor 2A) is a crucial tumor suppressor gene that encodes two important proteins, p16INK4a and p14ARF, which play significant roles in regulating the cell cycle and cellular responses to stress. <br> Its inactivation is a common event in many cancers, contributing to tumorigenesis and disease progression. <br> The status of CDKN2A can serve as a prognostic marker in various cancers. Loss of CDKN2A expression is often associated with poor prognosis and more aggressive disease.<br>
700-	CDX2	↑	Caudal-type homeobox 2		transcription factor	<b>CDX2 (Caudal-type homeobox 2)</b> is a transcription factor that plays a crucial role in the development and differentiation of the intestinal epithelium. In the context of cancer, CDX2 is often used as a diagnostic marker to help identify the primary site of origin for metastatic carcinomas.<br> Expressed in: CRC GI, Pancreatic, intestine, appendiceal, biliary, esophageal, ovarian, endometrial<br>
1056-	CEA	↑	Carcinoembryonic antigen		tumor marker	<b>Carcinoembryonic antigen (CEA)</b> is a glycoprotein involved in cell adhesion and is one of the most widely used tumor markers, especially in gastrointestinal malignancies. <br> <br> CEA is commonly overexpressed in several cancers, most notably colorectal cancer, but also in cancers of the lung, pancreas, breast, and others.<br> – Both tissue expression and serum CEA levels can be monitored; serum measurements are frequently used in clinical practice.<br>
54-	CEBPA	↓	CCAAT/enhancer binding protein (C/EBP), alpha	CGL-Driver Genes	TSG	<b>CEBPA (CCAAT/enhancer-binding protein alpha)</b> is a transcription factor that plays a significant role in regulating gene expression related to cell differentiation, proliferation, and metabolism. It is particularly important in the context of hematopoiesis (the formation of blood cells) and has been implicated in various cancers, especially acute myeloid leukemia (AML).<br> In general, altered expression of CEBPA, particularly downregulation, is often associated with more aggressive tumor behavior and poorer prognosis in various cancer types. <br>
1259-	CEBPB	↑	CCAAT/enhancer‐binding protein beta			<b>CCAAT/enhancer‐binding protein beta (CEBPB)</b><br> CEBPB is a transcription factor that regulates genes involved in proliferation, differentiation, immune responses, and inflammation.<br> <br> – In some contexts, high expression of CEBPB correlates with aggressive tumor behavior and poor clinical outcomes, whereas in other settings it might indicate a more differentiated state and, consequently, a less aggressive phenotype.<br> - CEBPB expression was obviously elevated in CRC patients, and was associated with poor survival.<br>
1234-	cellD	?	cell Death			<b>Cell Death</b><br>
532-	CellMemb	?	Cellular Membrane alterations			<b>The cell membrane,</b> also called the plasma membrane, is a thin layer that surrounds the cell. It is a selectively permeable cell organelle, allowing certain substances inside the cell while preventing others to pass.<br>
920-	cellSen	⇅	cellular senescence			<b>Cellular senescence</b> is a state in which cells cease to divide and grow, often in response to DNA damage or other forms of cellular stress.<br> On one hand, senescence can prevent cancer by:<br> -Halting the proliferation of damaged cells, thereby preventing the accumulation of mutations that can lead to cancer<br> -Activating immune responses that can eliminate senescent cells.<br> -Producing anti-tumor factors that can inhibit the growth of nearby cancer cells.<br> <br> On the other hand, senescence can also promote cancer by:<br> -Creating a pro-tumorigenic microenvironment that can support the growth of nearby cancer cells<br> -Producing pro-inflammatory factors that can promote cancer progression<br> -Contributing to the development of a senescence-associated secretory phenotype (SASP), which can promote cancer cell growth and metastasis.<br>
57-	CentClus	↑	Centrosome clustering	HalifaxProj(block)		<b>Centrosome Clustering in Cancer Cells:</b> To counteract the effects of centrosome amplification, cancer cells often employ centrosome clustering. By clustering multiple centrosomes, cancer cells can form a more stable bipolar spindle, which helps to maintain some level of proper chromosome segregation despite the presence of extra centrosomes. However, this is a temporary solution and does not fully resolve the underlying issues of genomic instability.<br> Many cancer cells exhibit centrosome amplification, where cells have more than two centrosomes.<br>
1220-	Ceru	↑	ceruloplasmin			<b>Ceruloplasmin</b> is primarily known as a copper-binding glycoprotein with roles in iron metabolism and antioxidant defense.<br> • Ceruloplasmin functions in copper transport and exhibits oxidase activity, which can help moderate oxidative stress.<br> • Its role in iron metabolism may further influence cellular redox balance and inflammatory processes.<br> <br> -In several cancer types (such as breast, lung, and colorectal cancers), elevated ceruloplasmin levels have been associated with more aggressive disease features and, in some studies, poorer prognosis.<br>
885-	cFLIP	↑	cellular FLICE-like inhibitory protein		protein	<b>c-FLIP (cellular FLICE-like inhibitory protein)</b> also know as FLIP<br> - is a protein that plays a crucial role in the regulation of apoptosis, or programmed cell death.<br> It is a key regulator of the extrinsic pathway of apoptosis, which is mediated by death receptors such as Fas and TNF-R1.<br> c-FLIP is a pseudokinase that can inhibit the activation of caspase-8, a key enzyme in the extrinsic pathway of apoptosis. By inhibiting caspase-8 activation, c-FLIP can prevent the initiation of the apoptotic cascade and promote cell survival.<br> In cancer, c-FLIP is often overexpressed, which can contribute to the development and progression of the disease.<br>
479-	cFos	↑	cellular Fos			<b>c-Fos</b> is an immediate early gene that encodes a protein involved in various cellular processes, including cell proliferation, differentiation, and survival. It is part of the Fos family of proteins, which are transcription factors that can regulate the expression of other genes. Increased expression of c-Fos is often associated with more aggressive tumor behavior and poorer prognosis across various cancer types. Its role as an immediate early gene suggests that it may be involved in the early response to oncogenic signals, contributing to tumor development and progression.<br>
1230-	ChemChap	?	chemical chaperones			<b>Chemical chaperones</b> are small molecules that assist proteins in folding correctly, thereby reducing misfolding and aggregation.<br> -Cancer cells often exhibit high levels of protein synthesis and stress on the protein-folding machinery (such as the endoplasmic reticulum, ER). Misfolded proteins can lead to ER stress and activate the unfolded protein response (UPR). Chemical chaperones can help alleviate this stress by assisting in proper protein folding and reducing aggregation, potentially affecting the survival and proliferation of cancer cells.<br> <br> -4-Phenylbutyric acid (4-PBA): One of the most extensively studied chemical chaperones, 4-PBA has been researched for its ability to reduce ER stress in various cellular models, including cancer. -Tauroursodeoxycholic acid (TUDCA): Another chemical chaperone that has been investigated for similar properties in alleviating ER stress.<br> <br> -Challenges: The dual role of the UPR in both cell survival and death means that the context of treatment is crucial. Moreover, systemic administration of chemical chaperones might affect normal tissues, so selectivity and dosing become important considerations.<br>
1171-	chemoP	∅	ChemoProtective			<b>Protects</b> normal cells against the effect of Chemo.<br>
1118-	chemoR	↑	chemoresistance			<b>Chemoresistance</b> refers to the ability of cancer cells to resist the effects of chemotherapy drugs, rendering treatments less effective or even ineffective. This resistance can be intrinsic (present before treatment) or acquired (developing during treatment) and poses a significant challenge in cancer therapy.<br> <br> Eight recognized mechanisms underlying chemoresistance:<br> 1.tumor heterogeneity; <br> 2.inactivation of drugs (cytochrome P450, glutathione-S-transferase (GST), uridine diphospho-glucuronosyltransferase (UGT) superfamily); <br> 3.overexpression of drug targets (EGFR and its downstream signaling targets); <br> 4.efflux pump overexpression (MDR or P-gp, MRP1, ABCG2);<br> 5.DNA damage repair; <br> 6.evasion of cell death mediated by Bcl-2, Akt, NF-κB and STAT; <br> 7.EMT favored by overexpression of TGF-β, FAK VEGF; and <br> 8.epigenetic changes.<br>
1106-	ChemoSen	↓	chemo-sensitization			<b>The effectiveness of chemotherapy</b> by increasing cancer cell sensitivity to the drugs used to treat them, which is known as “chemo-sensitization”.<br> <br> Chemo-Sensitizers:<br> -Curcumin<br> -Resveratrol<br> -EGCG<br> -Quercetin<br> -Genistein<br> -Berberine<br> -Piperine: alkaloid from black pepper<br> -Ginsenosides: active components of ginseng<br> -Silymarin<br> -Allicin<br> -Lycopene<br> -Ellagic acid<br>
784-	ChemoSideEff	↑	Side Effects of Chemo			<b>Refering</b> to the undesired side effects of treatments such as Chemotherapy.<br>
594-	CHK1	↑	Checkpoint Kinase 1			<b>A protein</b> that plays a crucial role in the DNA damage response pathway. It is involved in the repair of DNA damage and the maintenance of genome stability.<br> CHK1 acts as a tumor suppressor by preventing the accumulation of DNA damage and maintaining genome stability. Loss of CHK1 function can lead to increased genetic instability and a higher risk of cancer.<br> -CHK1 is often overexpressed in various types of cancer, including breast, colorectal, lung, and ovarian cancer. Overexpression of CHK1 can contribute to the development of resistance to chemotherapy and radiation therapy.<br> -CHK1 expression is often higher in tumor cells compared to normal cells. This tumor-specific expression makes CHK1 a potential target for cancer therapy.<br>
754-	Chk2	↓	Checkpoint Kinase 2		protein	<b>Chk2:</b> a protein that plays a crucial role in the regulation of the cell cycle and the response to DNA damage. It is a tumor suppressor gene that helps to prevent cancer by ensuring that cells with damaged DNA do not divide and proliferate.<br> Chk2 is activated in response to DNA damage, such as that caused by ionizing radiation or certain chemicals. Once activated, Chk2 phosphorylates and activates other proteins that help to repair DNA damage or induce cell death (apoptosis) if the damage is too severe.<br> Decreased expression or loss of function of CHK2 is often associated with more aggressive tumor behavior, increased invasiveness, and poorer prognosis across various cancer types. CHK2 plays a crucial role in maintaining genomic stability, and its dysfunction can lead to increased susceptibility to DNA damage and tumorigenesis.<br>
1204-	Chl	↑	chloride			<b>Chloride</b> ion channels and transporters encompass a diverse family of proteins that help regulate membrane potential, cell volume, and intracellular pH.<br> <br> -Chloride channels facilitate the movement of chloride ions across cell membranes, contributing to processes such as electrical signaling, regulation of cell volume, and maintenance of intracellular pH.<br> -They include several families and subtypes, such as the CLC family, volume-regulated anion channels (VRACs), and chloride intracellular channel (CLIC) proteins.<br> -These channels are involved in cell-cycle regulation, apoptosis, and migration—all processes that can influence tumor growth and metastasis.<br> <br> -Members of the CLC family (e.g., CLC-3) have been reported to be overexpressed in certain cancers like gliomas, breast cancer, and prostate cancer, where they may contribute to enhanced cellular proliferation and invasiveness.<br> -Chloride intracellular channel proteins (e.g., CLIC1) have been found to have increased expression in cancers including colorectal, lung, and ovarian carcinomas. Elevated levels of CLIC1, for instance, have been linked to increased tumor aggressiveness.<br>
470-	cholinesterase	↓	cholinesterase		enzyme	<b>Cholinesterase</b> is an enzyme that plays a crucial role in the nervous system by breaking down the neurotransmitter acetylcholine. <br> Some studies have found that cholinesterase inhibitors, which are compounds that block the activity of cholinesterase, may have anti-cancer effects. <br> Butyrylcholinesterase (BCHE) is a type of cholinesterase that has been found to be overexpressed in certain types of cancer, including breast, colon, and lung cancer.<br> Acetylcholinesterase (AChE) is another type of cholinesterase that has been found to be involved in the development and progression of certain types of cancer. Inhibitors of AChE have been shown to have anti-cancer effects in preclinical studies.<br> In general, alterations in cholinesterase activity, particularly AChE and BChE, can be associated with tumor behavior and prognosis in various cancer types. While high levels of cholinesterases may correlate with better outcomes in some cancers, the specific implications can vary depending on the cancer type and other molecular factors.<br> High AChE activity has been associated with better prognosis, while low activity may correlate with more aggressive disease.<br>
58-	CholMet	↑	Cholesterol metabolites	HalifaxProj(inhibit)		<b>Cholesterol metabolites</b> play significant roles in cancer biology, influencing processes such as cell proliferation, inflammation, and hormonal regulation. <br> Cholesterol metabolites can influence inflammatory processes, which are often associated with cancer progression. For instance, 27-hydroxycholesterol has been implicated in promoting inflammation in the tumor microenvironment, which can support tumor growth and metastasis.<br> certain cholesterol metabolites are often found at elevated levels or are dysregulated in various types of cancer.<br> 1. Oxysterols<br> Oxysterols are oxidized derivatives of cholesterol that can have various biological effects, including promoting cell proliferation and inflammation. <br> Certain oxysterols, such as 27-hydroxycholesterol, have been found to be elevated in various cancers, including breast cancer. This metabolite can promote tumor growth and metastasis by activating specific signaling pathways (e.g., the estrogen receptor pathway) and influencing the immune response.<br> 2. Steroid Hormones<br> Estrogens: In hormone-sensitive cancers, such as breast cancer, estrogen levels can be elevated due to increased conversion of cholesterol to estrogen. This can drive the growth of estrogen receptor-positive tumors.<br> Androgens: In prostate cancer, androgens derived from cholesterol can promote tumor growth. Elevated levels of androgens are often associated with advanced stages of prostate cancer. Increased Synthesis: Cancer cells often exhibit increased cholesterol synthesis to support their rapid growth and proliferation.<br>
59-	CholSyn	↑	Cholesterol synthesis	HalifaxProj(inhibit)		<b>Increased Synthesis:</b> Cancer cells often exhibit increased cholesterol synthesis to support their rapid growth and proliferation. This can lead to elevated levels of cholesterol and its metabolites.<br> Regulatory Enzymes: Enzymes involved in cholesterol metabolism, such as HMG-CoA reductase (the target of statins), may be overexpressed in certain cancers, contributing to altered cholesterol homeostasis.<br>
490-	CHOP	↑	GADD153		Protein	<b>GADD153 and CHOP </b>(C/EBP-homologous protein) refer to the same protein. GADD153 stands for "Growth Arrest and DNA Damage-inducible protein 153," while CHOP stands for "C/EBP Homologous Protein." <br> DDIT3 (DNA Damage Inducible Transcript 3), also known as CHOP (C/EBP Homologous Protein), is a transcription factor that plays a significant role in the cellular response to stress, particularly in the context of the unfolded protein response (UPR) and apoptosis.<br> <br> CHOP is an important component of the endoplasmic reticulum (ER) stress response. Research has shown that knockdown of CHOP not only enhances tunicamycin-induced autophagy, but also significantly attenuates ER stress-induced apoptosis in human colon cancer cells.<br> GADD153, also known as CHOP (C/EBP homologous protein), is a transcription factor that plays a significant role in cellular stress responses, particularly in the context of the endoplasmic reticulum (ER) stress response. It is part of the unfolded protein response (UPR), which is activated when there is an accumulation of misfolded proteins in the ER.<br>
60-	ChrMod	?	Chromatin modification	CGL-CF		<b>Genes</b> encode proteins that directly regulate chromatin through modification of histones or DNA. Examples include the histones HIST1H3B and H3F3A, as well as the proteins DNMT1 and TET1, which covalently modify DNA, EZH2, SETD2, and KDM6A, which, in turn, methylate or demethylate histones (53–57). <br> Chromatin modifications are critical regulators of gene expression and play significant roles in cancer development and progression. Dysregulation of these modifications can lead to the silencing of tumor suppressor genes, activation of oncogenes, and genomic instability.<br>
62-	CIC	↓	capicua homolog (Drosophila)	CGL-Driver Genes	TSG	<b>Capicua homolog (CIC)</b> is a transcriptional repressor that plays a significant role in regulating gene expression, particularly in the context of developmental processes and cellular responses to various signals. CIC is involved in several biological pathways, including those related to cell proliferation, differentiation, and apoptosis.<br> It is known to interact with various signaling pathways, including the receptor tyrosine kinase (RTK) and RAS signaling pathways.<br> CIC is often considered a tumor suppressor gene. Loss of CIC function or expression can lead to the activation of oncogenic pathways, promoting uncontrolled cell proliferation and tumorigenesis.<br> CIC is frequently mutated or deleted in several types of cancer, including glioblastoma, lung cancer, and certain hematological malignancies. These alterations can lead to the loss of its repressive function, resulting in the upregulation of target genes that promote tumor growth.<br> The expression levels of CIC can serve as a prognostic marker in certain cancers. Low levels of CIC expression have been associated with poor prognosis and more aggressive disease in some studies.<br> <br> CIC as a Gene (Capicua Transcriptional Repressor):<br> CIC acts as a tumor suppressor gene (TSG) in many contexts. Its loss or mutation—often identified in certain brain tumors and sarcomas—is considered a driver event in those cancers. By losing its normal function as a transcriptional repressor, abnormal expression of downstream genes can occur, contributing to cancer development.<br>
1154-	CIP2A	↑	Cancerous Inhibitor of Protein Phosphatase 2A			<b>Cancerous Inhibitor of Protein Phosphatase 2A (CIP2A)</b> is an oncoprotein that plays a critical role in promoting tumorigenesis by inhibiting the activity of protein phosphatase 2A (PP2A), a tumor suppressor. <br> <br> -CIP2A inhibits PP2A, leading to sustained activation of oncogenic signaling pathways such as AKT, MYC, and others that drive cell proliferation, survival, and growth.<br> -By stabilizing these oncoproteins, CIP2A contributes to tumor initiation, progression, and resistance to apoptosis.<br> <br> <br> -CIP2A is frequently overexpressed in various cancers, including breast, lung, colorectal, and head and neck cancers, among others.<br> -Elevated CIP2A expression promotes the malignant phenotype by deregulating key pathways that control cell cycle progression and survival.<br> <br> <br> -High CIP2A levels are generally associated with a poor prognosis. Increased expression often correlates with more aggressive tumor behavior, higher rates of metastasis, and reduced overall survival.<br> -In many cancer types, CIP2A overexpression is considered an independent prognostic marker, indicating a greater likelihood of treatment resistance and disease recurrence.<br>
668-	circ-PRKCA	↑	circular RNA PRKCA		Oncogene	<b>Circ-PRKCA (circular RNA PRKCA)</b> is a type of circular RNA that has been implicated in various types of cancer. Circular RNAs (circRNAs) are a class of non-coding RNAs that are characterized by their covalently closed loop structure.<br> <br> Research has shown that circ-PRKCA is overexpressed in several types of cancer.<br> Overexpressed: CRC, Breast, lung, ovarian<br> <br> Overall, the available evidence suggests that circ-PRKCA is a potential oncogene that promotes cancer development and progression.<br>
951-	citrate	↓	citrate levels			<b>Citrate</b> is a key metabolite involved in cellular energy metabolism, and its levels are often elevated cancer cells. <br> -Citrate is a key substrate for the citric acid cycle (also known as the Krebs cycle or tricarboxylic acid cycle), which is involved in cellular energy metabolism.<br> -Citrate is also involved in the regulation of glycolysis, which is the primary source of energy for many cancer cells.<br> -Citrate has been shown to promote cancer cell growth and survival by regulating various signaling pathways, including the PI3K/AKT pathway.<br> <br> High citrate levels are often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, ovarian, and glioblastoma.<br> – Several studies have reported that in certain aggressive tumors, intracellular citrate levels tend to be lower relative to adjacent normal tissues. This is thought to be due to increased utilization of citrate for anabolic processes (e.g., fatty acid synthesis).<br> <br> It was found that the citrate levels of normal human prostate tissue are uniquely much higher than those in malignant prostate tissue (43.1 versus 19.9 mmol/kg). Furthermore, the drastic decrease of citrate level (up to 40-fold in early and 80-fold in advanced stages) in prostate cancer tissues in comparison to normal prostatic tissues is a key characteristic utilized to distinguish between normal and hyperplastic glands. In addition to prostate cancer, citrate levels are significantly decreased in blood of patients with lung, bladder, pancreas and esophagus cancers compared with healthy persons.<br> As a consequence, normal prostate has high concentrations of citrate whereas prostate cancer has low concentrations of citrate.<br> <br> It was widely believed that cancer cells did not take up citrate from the circulation (blood levels of citrate, ~200 μM) and that they met their increased demands for this metabolite via de no synthesis from glutamine (Metallo et al., 2011). This requires a novel reprogramming of the metabolism involving the reversal of the Krebs cycle in which α-ketoglutarate arising from glutamine gets converted into citrate by a process known as “reductive carboxylation.” Indeed, uptake of glutamine resulting from increased expression of multiple glutamine transporters has been associated with cancer cells.<br> <br> Citrate is not only a metabolic intermediate but also a critical signaling node that affects epigenetic regulation (via acetyl-CoA), lipogenesis, and cellular survival pathways. The expression levels of ACLY, SLC25A1, IDH1/2, FASN, and SREBF1 have emerged as important prognostic biomarkers or therapeutic targets in various cancers.<br> <br> -Lower plasma citrate levels have been observed in some cancer patients, suggesting that the tumor’s high metabolic demand may deplete circulating citrate.<br> <br> While many tumors show reduced tissue citrate due to its rapid utilization in anabolic pathways, circulating citrate levels can also be altered, potentially serving as noninvasive biomarkers.<br> In those relying on an oxidative metabolism, fatty acid β-oxidation sustains a high production of citrate, which is still rapidly converted into acetyl-CoA and oxaloacetate, this latter molecule sustaining nucleotide synthesis and gluconeogenesis. Therefore, citrate levels are rarely high in cancer cells.<br> <br> Citrate is a gauge of nutrients available for biosynthesis and ATP production generated via oxidative phosphorylation (OXPHOS). In addition, citrate is a key regulatory molecule, which targets (directly or indirectly) catabolic and anabolic pathways (fatty acid β-oxidation (FAO) and FAS, glycolysis, and gluconeogenesis) in a manner such that when one pathway is activated, the other is inhibited. For example, citrate directly inhibits the main regulators of glycolysis, phosphofructokinase-1 (PFK1) and phosphofructokinase-2 (PFK2) [2,3], while it enhances gluconeogenesis by promoting fructose-1,6-biphosphatase (FBPase).<br> <br> <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8235534/"> Hypothesis that a low citrate level promotes the Warburg effect. </a> <br>
34-	cJun	↑	cellular Transcription factor Jun		Oncogene	<b>Transcription factor Jun</b> is a protein that in humans is encoded by the JUN gene. <br> Increased c-jun gene and c-Jun protein expression, and stimulation of c-Jun phosphorylation has been noted under a variety of conditions. Most important member of the AP-1 transcription factor family.<br>
524-	CK2	↑	Casein Kinase 2			<b>CK2,</b> or Casein Kinase 2, is a serine/threonine kinase that plays a significant role in various cellular processes, including cell growth, proliferation, and survival. Research has shown that CK2 is often overexpressed in various types of cancer, and its activity is associated with tumor progression and resistance to apoptosis (programmed cell death).<br> <br> -casein kinase 2 (CK2) is a positive regulator in the self-renewal of cervical cancer stem-like cells<br>
968-	CLDN1	↑	claudin-1		gene	<b>The CLDN1 gene (Claudin-1)</b> is a tight junction protein that plays a crucial role in maintaining epithelial barrier function and regulating cell-cell adhesion.<br> <br> Breast cancer: Elevated in 50% of breast cancer, associated with poor prognosis <br> Lung cancer: Elevated in 60% of lung cancer tissues, associated with poor prognosis<br> Colorectal cancer: Elevated in 70%, associated with poor prognosis<br> Prostate cancer: REDUCED in 40%, and associated with poor prognosis<br> Ovarian cancer: Elevated in 55%, associated with poor prognosis<br> Gastric cancer:Elevated in 60%, associated with poor prognosis<br> Hepatocellular carcinoma:Elevated in 65%, associated with poor prognosis<br> Pancreatic cancer: Elevated in 75%, associated with poor prognosis<br>
1163-	CLDN2	↑	claudin-2			<b>Claudin-2</b> is a member of the claudin family of tight junction proteins that regulate paracellular permeability and influence cell signaling.<br> <br> • High expression of CLDN2 has been associated in several studies with enhanced tumor aggressiveness, increased invasiveness, and, in some cancers (e.g., colorectal and hepatocellular carcinoma), poorer prognostic outcomes.<br>
61-	CLDN3	↑	claudin‑3			<b>Claudin-3</b> is a member of the claudin family of proteins, which are integral components of tight junctions in epithelial cells. Tight junctions are crucial for maintaining the integrity of epithelial barriers, regulating paracellular permeability, and facilitating cell signaling.<br> Claudin-3, in particular, has been studied for its role in various cancers, and its expression levels can have significant implications for tumor behavior and patient prognosis. <br> Role of Claudin-3<br> Tight Junction Formation: Claudin-3 is involved in the formation of tight junctions, which help to maintain cell polarity and barrier function in epithelial tissues. It plays a role in regulating the permeability of the epithelial barrier.<br> Cell Signaling: Beyond its structural role, claudin-3 can participate in signaling pathways that influence cell proliferation, differentiation, and apoptosis.<br> Expression Patterns:<br> Overexpression: Claudin-3 is often found to be overexpressed in various cancers, including breast cancer, ovarian cancer, and pancreatic cancer. This overexpression can contribute to tumor progression and metastasis.<br> Loss of Expression: In some contexts, loss of claudin-3 expression can also be observed, particularly in more aggressive tumor types. This loss can disrupt tight junction integrity and promote invasiveness.<br>
1193-	CLP	↓	bone marrow common lymphoid progenitor cells			<b>Bone marrow common lymphoid progenitor (CLP) cells.</b> <br> • CLPs are a population within the bone marrow that give rise to multiple lymphoid lineages, including B cells, T cells, and natural killer (NK) <br> <br> • In the setting of bone marrow transplantation or immune reconstitution (for instance, after chemotherapy), the recovery of CLP populations can serve as a marker of effective hematopoietic regeneration.<br>
484-	cMET	↑	cellular hepatocyte growth factor receptor			<b>c-MET,</b> also known as the hepatocyte growth factor receptor (HGFR), is a receptor tyrosine kinase that plays a crucial role in various cellular processes, including cell proliferation, survival, migration, and differentiation. It is activated by its ligand, hepatocyte growth factor (HGF). Dysregulation of the c-MET signaling pathway has been implicated in several types of cancer.<br> <br> c-Met is often overexpressed or mutated in cancer and is associated with poor prognosis, increased metastasis, and resistance to therapies.<br>
1077-	cMYB	↑	c-MYB		marker	<b>c‑MYB</b> is a transcription factor that plays critical roles in cell proliferation, differentiation, and apoptosis. <br> – c‑MYB is a transcription factor essential for normal hematopoiesis and the regulation of genes involved in cell cycle progression, differentiation, and survival.<br> <br> – Aberrant or sustained expression of c‑MYB is found in several malignancies, particularly hematological cancers such as acute leukemias, as well as solid tumors including breast and colon cancers.<br> – Overexpression or mutation of c‑MYB can lead to enhanced cell proliferation and impaired differentiation, creating an environment conducive to malignant transformation and tumor maintenance.<br> – In several studies, high levels of c‑MYB correlate with more aggressive tumor behavior and poorer clinical outcomes, such as reduced overall survival and an increased likelihood of relapse.<br> <br> c‑MYB plays a pivotal role in the regulation of cell proliferation, differentiation, and survival. Its dysregulation in cancer contributes to unchecked growth and resistance to cell death, correlating with aggressive disease and poorer clinical outcomes.<br>
35-	cMyc	↑	cellular-MYC oncogene		oncogene	<b>The MYC proto-oncogenes</b> are among the most commonly activated proteins in human cancer. The oncogene c-myc, which is frequently over-expressed in cancer cells, is involved in the transactivation of most of the glycolytic enzymes including lactate dehydrogenase A (LDHA) and the glucose transporter GLUT1 [51,52]. Thus, c-myc activation is a likely candidate to promote the enhanced glucose uptake and lactate release in the proliferating cancer cell. The c-Myc oncogene is a ‘master regulator’ of both cellular growth and metabolism in transformed cells.<br> -C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A<br> <br> Inhibitors (downregulate):<br> Curcumin<br> Resveratrol: downregulate c-Myc expression.<br> Epigallocatechin Gallate (EGCG)<br> Quercetin<br> Berberine: decrease c-Myc expression and repress its transcriptional activity.<br>
1013-	Cofilin	⇅	Cofilin			<b>Cofilin</b> is an actin-binding protein that plays a central role in regulating actin dynamics and cytoskeletal remodeling. Its activity is essential for various cellular functions, including migration, invasion, and cell division.<br> <br> High levels of active cofilin have been associated with increased invasiveness and metastatic potential in several tumor types, often correlating with a poorer prognosis. Assessing cofilin activity (for example, via levels of phosphorylated vs. non-phosphorylated protein) might provide insights into the metastatic potential of a tumor.<br>
557-	cognitive	?	cognitive			<b>Cognitive</b> <br>
1004-	COL1	↑	Collagen I			<b>Collagen I,</b> primarily composed of two chains encoded by the genes COL1A1 and COL1A2.<br> - Collagen I is the most abundant collagen in the human body and is a major component of the extracellular matrix (ECM), providing structural support to tissues.<br> - It is typically a heterotrimer composed of two α1(I) chains (COL1A1) and one α2(I) chain (COL1A2).<br> <br> - Cancer progression is often accompanied by significant remodeling of the ECM.<br> - Collagen I deposition frequently increases in many solid tumors, contributing to a dense and fibrotic stroma (desmoplasia).<br> - Increased collagen I deposition can lead to higher ECM stiffness, which in turn modifies cell signaling and behavior.<br> <br> Expression Patterns:<br> - Tumors such as breast, pancreatic, colorectal, and lung cancers often exhibit elevated levels of collagen I.<br> - High collagen I expression or deposition in the tumor stroma is frequently correlated with a more aggressive tumor phenotype.<br>
864-	COL1A1	↑	Collagen Type I Alpha 1 Chain		gene/protein	<b>COL1A1 (Collagen Type I Alpha 1 Chain)</b> is a gene that encodes for a protein that is a component of type I collagen, a major structural protein found in the extracellular matrix of connective tissue.<br> COL1A1 has been shown to promote tumor growth, invasion, and metastasis by facilitating cell adhesion, migration, and angiogenesis.<br>
422-	COL2A1	↑	COL2A1		gene	<b>The COL2A1 gene</b> is a gene that encodes for the pro-alpha1(II) chain of type II collagen, a protein that is a major component of cartilage. While the primary function of COL2A1 is related to cartilage development and maintenance, research has also explored its potential role in cancer. Overexpressed in: Osteosarcoma, chondrosarcoma, breast, lung.<br> COL2A1 may facilitate the migration and invasion of tumor cells by interacting with other proteins and promoting the degradation of the extracellular matrix.<br>
1057-	COL3A1	↑	collagen3a			<b>COL3A1</b> encodes a component of type III collagen—a major structural protein in the extracellular matrix.<br> <br> Elevated COL3A1 expression has frequently been observed in solid tumors and is often associated with a desmoplastic response.<br> There is a recurring observation across multiple tumor types that increased COL3A1 expression in the tumor stroma is linked to worse clinical outcomes, including more advanced stage and lower survival rates.<br>
546-	COL4	↑	Collagen IV alpha chain			<b>Family</b> is a major component of the basement membrane (BM) that has recently been found to be involved in tumor angiogenesis and progression.<br> Type IV collagen, an important component of the basement membrane, is highly expressed by pancreatic cancer cells both in vivo and in vitro. <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC3618250/">The interaction between type IV collagen produced by the cancer cell, and integrins on the surface of the cancer cells, are important for continuous cancer cell growth, maintenance of a migratory phenotype, and for avoiding apoptosis. </a> <br>
523-	COL9A3	↓	COL9A3		gene	<b>The COL9A3 gene</b> is a type of collagen gene that encodes for the alpha 3 chain of type IX collagen. Type IX collagen is a type of fibril-associated collagen with interrupted triple helices (FACIT) collagen, which is a component of cartilage and other connective tissues.<br> COL9A3 has been identified as a potential tumor suppressor gene in breast cancer, with reduced expression levels observed in breast cancer tissues.<br>
486-	COMP	↑	Cartilage Oligomeric Matrix Protein		gene	<b>The COMP</b> gene (Cartilage Oligomeric Matrix Protein) is a gene that encodes a protein involved in the formation and maintenance of cartilage. While COMP is not typically considered a tumor suppressor gene or an oncogene, mutations in the COMP gene have been associated with various types of cancer.<br> COMP is overexpressed in certain types of cancer, including: Osteosarcoma (bone cancer), Chondrosarcoma (cartilage cancer), Breast, Lung, CRC.<br>
1228-	compI	⇅	mitochondrial complex-I			<b>Mitochondrial complex I</b> (NADH:ubiquinone oxidoreductase) is the largest enzyme of the oxidative phosphorylation system. Its function is essential for bioenergetics and redox balance. Altered expression of its subunits can lead to changes in tumor metabolism, reactive oxygen species (ROS) generation, and apoptotic sensitivity—all of which may impact tumor growth and patient outcomes.<br> <br> Commonly Reported Complex I Subunit:<br> -Increased expression of NDUFA4L2 has been associated with poor prognosis<br> -Reduced expression of core complex I subunits (such as NDUFS1 and NDUFS3) may correlate with a poorer overall survival in some cancers <br> -NDUFV1 have been linked to adverse clinical outcomes<br> <br> -Dysregulation of complex I may alter ROS production. In some cancers, controlled ROS production can aid in signaling that promotes cell proliferation or survival, while excessive ROS can trigger cell death. Genes like NDUFA4L2 are also linked with hypoxia, a common feature in the tumor microenvironment.<br>
1070-	compIII	↑	Mitochondrial complex III			<b>Complex III</b> is part of the mitochondrial respiratory chain. It plays a key role in oxidative phosphorylation by transferring electrons from ubiquinol (coenzyme Q) to cytochrome c.<br> • The complex is made up of multiple subunits. In humans, some of the key proteins include:<br> -UQCRC1 (ubiquinol-cytochrome c reductase core protein I)<br> -UQCRC2 (core protein II)<br> -UQCRFS1 (the Rieske iron-sulfur protein)<br> -UQCRB (cytochrome b)<br> <br> Complex III is a significant source of reactive oxygen species (ROS) when electron transport is inefficient. Increased ROS can promote DNA damage and genomic instability, factors known to drive cancer progression.<br> Expression levels of Complex III subunits, particularly UQCRFS1 and UQCRC1, have been evaluated as biomarkers. High expression may suggest a more aggressive tumor phenotype, thus linking mitochondrial respiratory chain activity with clinical outcomes.<br>
64-	COMT	?	catechol-O-methyl transferase			<b>Catechol-O-methyltransferase (COMT)</b> is an enzyme located in the frontal cortex of the brain that metabolizes epinephrine, norepinephrine, and dopamine.<br> Genetic polymorphisms in the COMT gene can influence enzyme activity and may be associated with the risk of certain cancers. <br> COMT is involved in the metabolism of estrogens, particularly catechol estrogens, which can have both proliferative and genotoxic effects on breast tissue. Dysregulation of estrogen metabolism has been implicated in the development of hormone-related cancers.<br>
65-	Copper	↑				<b>Copper</b> is an essential trace element that plays a critical role in various biological processes, including iron metabolism, energy production, and the functioning of the immune system. However, its relationship with cancer is complex, as both copper deficiency and excess can influence cancer development and progression. <br> Many cancer cells exhibit elevated levels of copper compared to normal cells. This accumulation can support tumor growth and metastasis by:<br> Enhancing angiogenesis (the formation of new blood vessels).<br> Promoting cell proliferation and survival.<br> Supporting the activity of copper-dependent enzymes that facilitate tumor progression. Copper and Oxidative Stress: While copper is essential for antioxidant enzymes, excess copper can lead to the generation of reactive oxygen species (ROS), contributing to oxidative stress.<br> Elevated copper levels can promote inflammation and support the growth of tumors.<br> Copper Chelation Therapy: Given the role of copper in cancer progression, copper chelation (the use of agents that bind copper and promote its excretion) has been explored as a potential therapeutic strategy.<br>
1315-	CoQ10	↓	coenzyme Q10			<b>CoQ10 (coenzyme Q10)</b> is most widely recognized for its role in mitochondrial bioenergetics and antioxidant defense.<br> <br> -It functions as a potent antioxidant, protecting cells from oxidative damage and lipid peroxidation.<br> <br> -Some studies have suggested that low circulating CoQ10 levels in cancer patients (for example, in breast or colorectal cancer) might be associated with more aggressive disease or poorer overall health status.<br>
882-	cortisol	↑	cortisol			<b>Hormones</b> such as glucagon and cortisol can stimulate gluconeogenesis. In cancer, the dysregulation of these hormones can contribute to altered glucose metabolism.<br> Cortisol is a steroid hormone produced by the adrenal glands, primarily in response to stress and low blood glucose levels. <br> <br> Elevated cortisol levels have been observed in patients with cancer.<br> High cortisol levels may be associated with worse prognosis, increased tumor aggressiveness, and higher rates of metastasis. Chronic stress and elevated cortisol can influence tumor microenvironments.<br>
998-	COX1	↑	COX-1			<b>COX‑1</b> is traditionally considered a constitutively expressed enzyme involved in “housekeeping” functions, while COX‑2 is more frequently studied in relation to cancer.<br> • The prognostic impact of COX‑1 may vary based on cancer subtype, stage, and interplay with other inflammatory mediators (e.g., COX‑2).<br> • Many studies assess combined cyclooxygenase profiles (COX‑1/COX‑2) rather than COX‑1 alone.<br>
66-	COX2	↑	cycloocygenase-2 (Cox-2) mRNA and Cox-2 protein	HalifaxProj(inhibit)		<b>Cyclooxygenase-2 (COX-2)</b> is an enzyme that plays a critical role in the conversion of arachidonic acid to prostaglandins, which are lipid compounds involved in various physiological processes, including <b>inflammation</b>, pain, and fever. COX-2 is an inducible enzyme, meaning its expression is typically low in normal tissues but can be upregulated in response to inflammatory stimuli, growth factors, and certain oncogenic signals. <br> -Cyclooxygenase-2 (COX-2), the rate-limiting enzyme in prostaglandin biosynthesis, plays a key role in inflammation and circulatory homeostasis.<br> -COX-2 is an inducible enzyme that is upregulated in response to pro-inflammatory signals, including cytokines (e.g., IL-1β, TNF-α) and growth factors.<br> <br> COX-2 is often overexpressed in various tumors, including colorectal, breast, lung, and prostate cancers.<br> The prostaglandins produced by COX-2, particularly prostaglandin E2 (PGE2), have several effects that can facilitate cancer progression:<br> Cell Proliferation: PGE2 can promote the proliferation of cancer cells by activating signaling pathways such as the PI3K/Akt and MAPK pathways.<br> Nonselective NSAIDs, such as aspirin and ibuprofen, inhibit both COX-1 and COX-2. Epidemiological studies have suggested that regular use of NSAIDs may reduce the risk of certain cancers, particularly colorectal cancer. <br> Drugs specifically targeting COX-2, such as celecoxib, have been developed.<br> <br> COX-2 and xanthine oxidase are ROS-producing pro-oxidant enzymes that contribute to inflammation. Elevated COX‑2 levels, often found in inflammatory conditions or certain types of cancers, can contribute to increased production of ROS.<br>
1027-	cPLA2	↑	cytosolic phospholipase A2			<b>cPLA2</b> is a key enzyme that hydrolyzes membrane phospholipids to release arachidonic acid, serving as the precursor for the synthesis of eicosanoids (prostaglandins, leukotrienes, etc.). <br>These lipid mediators can significantly influence inflammation, cell proliferation, survival, angiogenesis, and metastasis—all processes that are critical in cancer development and progression.<br> <br> cPLA2 plays a multifaceted role in carcinogenesis through its involvement in the production of bioactive lipids that regulate inflammation, cell growth, and metastasis. Its expression is frequently elevated in several cancers—including breast, prostate, colorectal, lung, ovarian, and head and neck cancers—and is generally associated with a poorer prognosis.<br>
956-	CPT1A	↑	Carnitine Palmitoyltransferase 1A			<b>Carnitine Palmitoyltransferase 1A (CPT1A)</b> is an enzyme that plays a crucial role in the regulation of fatty acid metabolism, particularly in the transport of long-chain fatty acids into mitochondria for beta-oxidation. In cancer, CPT1A has been implicated in the regulation of tumor cell metabolism, proliferation, and survival. <br> <br> CPT1A typically overexpressed and is associated with poor prognosis and reduced overall survival in breast, lung, and colon cancers.<br> CPT1A expression is also associated with increased risk of metastasis and recurrence in various types of cancer.<br>
1140-	CR3	⇅	Complement Receptor Type 3			<b>Complement Receptor Type 3 (CR‐3),</b> also known as Mac-1 or integrin αMβ2<br> CR‐3 is mainly expressed on immune cells such as macrophages, neutrophils, and natural killer (NK) cells and plays a role in immune complex clearance, cell adhesion, and phagocytosis. <br> <br> – CR‐3 is critical in mediating phagocytosis, cytotoxicity, and the clearance of opsonized pathogens and cellular debris.<br> – In the tumor microenvironment, CR‐3–expressing immune cells can contribute to both anti-tumor responses and, in some contexts, protumoral inflammation.<br> <br> – The expression or activation state of CR‐3 on tumor-associated immune cells has been studied as a potential marker of the immune microenvironment’s status.<br> – In some reports, a higher presence or activation of CR‐3–positive immune cells correlates with more effective immune surveillance and better outcomes, suggesting an anti-tumor role.<br> – Conversely, if CR‐3 engagement promotes a protumoral inflammatory milieu (for example, by favoring the accumulation of immunosuppressive or M2-type macrophages), then higher CR‐3 activity may be associated with poorer prognosis.<br>
1251-	creat	↑	creatinine			<b>Creatinine</b> is fundamentally a metabolic waste product derived from creatine phosphate in muscle. Its blood levels are routinely used as a clinical biomarker to assess kidney function rather than a direct regulator of oncogenic processes.<br> Creatinine is a primary marker used to estimate the glomerular filtration rate (GFR).<br> <br> -Elevated creatinine can be a sign of compromised kidney vascular function.<br>
798-	CREB	↑	cAMP Response Element Binding Protein		transcription factor	<b>CREB</b> is a transcription factor that binds to specific DNA sequences, known as cAMP response elements (CRE), in the promoter regions of target genes.<br> CREB is activated by phosphorylation, which allows it to bind to CRE and recruit other transcriptional coactivators.<br> CREB regulates the expression of genes involved in various cellular processes, including:<br>     Cell growth and differentiation<br>     Apoptosis<br>     Metabolism<br>     Neurotransmission<br> <br> CREB is also involved in the regulation of genes involved in cancer, including:<br>     Cell cycle progression<br>     Angiogenesis<br>     Invasion and metastasis<br> <br> CREB is often overexpressed in cancer tissues.<br> High levels of CREB expression are associated with poor prognosis, increased tumor aggressiveness, and resistance to therapy. CREB can promote the expression of genes involved in cell survival and proliferation.<br>
991-	CREB2	⇅	cAMP response element‐binding protein 2			<b>CREB2 (cAMP response element‐binding protein 2)</b> is a member of the CREB/ATF family of transcription factors.<br> – CREB2 is involved in stress-related signaling pathways and has been implicated in processes like memory consolidation and synaptic plasticity in neuronal cells.<br> – It helps in the cellular response to environmental and intracellular stresses by modulating the expression of target genes.<br> – Through regulation of gene expression, CREB2 can influence proliferation, differentiation, and apoptosis in various cell types.<br> – The balance of CREB2 activity is critical in maintaining normal cellular homeostasis.<br> <br> – Some studies have reported increased CREB2 expression in certain cancers (e.g., brain tumors, leukemia), while others have noted reduced expression in different tumor types.<br>
67-	CREBBP	⇅	CREB binding protein	CGL-Driver Genes	TSG	<b>CREB-binding protein (CBP)</b> is a multifunctional coactivator that plays a crucial role in the regulation of gene expression. It interacts with various transcription factors, including the cAMP response element-binding protein (CREB), and is involved in numerous cellular processes, such as cell growth, differentiation, and apoptosis. <br> CBP can act as a tumor suppressor. For example, it can mediate the transcriptional activation of genes that promote apoptosis or inhibit cell proliferation. Loss of CBP function can lead to decreased expression of these protective genes, contributing to cancer progression.<br> CBP interacts with several oncogenic signaling pathways, including:<br> Wnt/β-catenin Pathway: CBP is a coactivator for β-catenin, a key player in the Wnt signaling pathway, which is often dysregulated in cancers. <br> CBP is also involved in the Hedgehog signaling pathway, which is important for embryonic development and has been implicated in the growth of certain tumors.<br> The expression of CREB-binding protein (CBP) in cancer is complex, with both overexpression and loss of function observed in different cancer types.<br>
68-	CRLF2	↑	cytokine receptor-like factor 2	CGL-Driver Genes	Oncogene	<b>Cytokine receptor-like factor 2 (CRLF2)</b> is a member of the cytokine receptor family and has been implicated in various biological processes, including immune responses and hematopoiesis.<br> CRLF2 has been associated with certain types of leukemia, particularly B-cell acute lymphoblastic leukemia (B-ALL). Abnormal expression or mutations in CRLF2 can lead to dysregulated signaling pathways that promote cell proliferation and survival, contributing to the development and progression of these cancers.<br> High levels of CRLF2 expression may correlate with poor outcomes in patients with specific types of leukemia.<br>
1128-	CRM	∅	Calorie restriction mimetics (CRMs)			<b>Calorie restriction mimetics (CRMs)</b> are compounds that appear to mimic some of the biochemical effects of caloric restriction without the need to actually reduce caloric intake.<br> <br> -Resveratrol:Known for activating sirtuins (e.g., SIRT1) <br> -Curcumin<br> -Quercetin<br> -EGCG<br> -Spermidine<br> -Fisetin<br> -Berberine<br> -Pterostilbene<br> -Hydroxytyrosol<br> -Sulforaphane<br> -Cinnamaldehyde<br> -Nicotinamide Riboside (NR) and Nicotinamide Mononucleotide (NMN)<br> -Alpha-Ketoglutarate (AKG)<br> -Rapamycin (Sirolimus<br>
227-	CRM1	↑	Nuclear exporter CRM1	HalifaxProj(inhibit)		<b>CRM1 (Chromosome Region Maintenance 1)</b> is a protein that plays a crucial role in the nuclear export of proteins and RNA. <br> CRM1 can influence the localization of tumor suppressor proteins and oncogenes. For example, the export of tumor suppressor proteins like p53 from the nucleus can lead to reduced tumor suppression, promoting cancer cell growth and survival.<br> CRM1 is often overexpressed in various types of cancers, including breast cancer, colorectal cancer, and leukemia. This overexpression can correlate with poor prognosis and aggressive tumor behavior.<br>
884-	CRP	↑	C-reactive protein			<b>C-Reactive Protein (CRP)</b> is a protein produced by the liver in response to inflammation in the body.<br>
1149-	CRT	↑	calreticulin			<b>Calreticulin (CRT)</b> is a multifunctional protein principally located in the endoplasmic reticulum (ER), where it plays key roles in calcium homeostasis, protein folding, and quality control. It has also emerged as an important player in cancer biology and immunogenic cell death.<br> <br> CRT expression can be upregulated in certain cancers, where it may be associated with an active unfolded protein response (UPR) or stress conditions in the tumor microenvironment.<br> <br> -In some cancers, elevated CRT expression has been correlated with improved outcomes due to its role in enhancing immunogenic cell death. For instance, when CRT is externalized on the surface of dying tumor cells, it can facilitate a robust anti-tumor immune response.<br> -Conversely, in other cancer types, high CRT levels may be associated with tumor progression, metastasis, or poor clinical outcomes—likely because CRT might also contribute to tumor cell migration or cell survival under stressful conditions.<br>
795-	CSCs	↑	Cancer Stem Cells			<b>Cancer Stem Cells</b><br>
796-	CSCsMark	↑	Cancer Stem Cell Markers			<b>CSC markers</b> include nanog, sox2, and oct3/4<br> CSC markers: CD55, CD133, ALDH1, SOX2, OCT4, NANOG, BMI1, ABCG2, CD24, EpCAM<br>
69-	CSF1R	↑	colony stimulating factor 1 receptor	CGL-Driver Genes	Oncogene	<b>Colony Stimulating Factor 1 Receptor (CSF1R)</b>, also known as the macrophage colony-stimulating factor receptor (M-CSFR), is a receptor that plays a crucial role in the regulation of macrophage development, survival, and function. Its involvement in cancer has been increasingly recognized, particularly in the context of the tumor microenvironment and immune modulation. <br> CSF1R signaling can lead to the accumulation of tumor-associated macrophages (TAMs), which often exhibit an immunosuppressive phenotype that supports tumor growth and metastasis.<br> Inhibitors of CSF1R are being developed and tested in clinical trials to deplete TAMs or block their recruitment, with the aim of enhancing anti-tumor immunity and improving the efficacy of existing therapies.<br> CSF1R expression levels in tumors may serve as a biomarker for prognosis or response to therapy. High levels of CSF1R and associated TAMs have been correlated with poor outcomes in various cancers, including breast cancer, ovarian cancer, and glioblastoma.<br>
405-	CSR1	?	Cellular stress response 1		tumor suppressor gene	<b>CSR1</b> is a tumor suppressor gene that was frequently down-regulated in prostate cancer(PCa). CSR1 has critical roles in the regulation of cell apoptosis via inactivation of CPSF3 or preventing the interaction of XIAP with caspases.<br>
36-	cSrc	↑	cellular Proto-oncogene tyrosine-protein kinase Src			<b>Proto-oncogene tyrosine-protein kinase Src,</b> also known as proto-oncogene c-Src, or simply c-Src, is a non-receptor tyrosine kinase protein that in humans is encoded by the SRC gene. <br> The product of the human SRC gene, c-Src, is found to be over-expressed and highly activated in a wide variety of human cancers.<br>
650-	CT-I	↑	Chymotrypsin-like (CT-l) activity			<b>Chymotrypsin-like (CT-l)</b> activity is a type of protease activity that is associated with certain types of cancer. Proteases are enzymes that break down proteins, and CT-l activity is a measure of the level of this type of protease activity in a given sample.<br> CT-l activity is often elevated, and this has been linked to a number of negative outcomes, including increased tumor growth and metastasis. As a result, CT-l activity is often used as a biomarker for cancer, and it may also be a target for cancer therapy.<br>
446-	CTC	↑	Circulating-Tumour-Cells			<b>CTC</b> provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission.<br>
211-	CTGF	↑	Connective Tissue Growth Factor		prognostic biomarker	<b>CTGF</b> is a matricellular protein that belongs to the CCN (Cyr61/CTGF/Nov) family. It plays a pivotal role in diverse biological processes, including cell adhesion, migration, proliferation, and differentiation. CTGF is also involved in wound healing and fibrosis. In cancer, CTGF’s function is multifaceted, affecting tumor growth, angiogenesis, and the remodeling of the tumor microenvironment.<br> <br> CTGF is overexpressed in several cancer types, such as pancreatic, breast, and prostate cancers. In these contexts, higher levels of CTGF have been associated with enhanced tumor growth, angiogenesis, and metastasis.<br> <br> Elevated CTGF expression often correlates with adverse clinical features.<br>
1031-	CTLA-4	↑	Cytotoxic T-Lymphocyte Antigen‑4			<b>CTLA-4</b> is a key immune checkpoint molecule that plays an important role in downregulating immune responses and maintaining self-tolerance. Its modulation has critical implications in cancer immunotherapy.<br> CTLA-4 is primarily expressed on activated T cells (and constitutively on regulatory T cells), where it functions as a negative regulator of T-cell immune responses.<br> CTLA-4 has been one of the first immune checkpoint molecules targeted in cancer therapy.<br> – Blockade of CTLA-4 (e.g., with ipilimumab) can enhance T-cell activation and restore antitumor immunity, leading to durable responses in certain cancer types such as melanoma.<br> <br> Cancers such as melanoma, NSCLC, RCC, colorectal cancer, HNSCC, and certain hematologic malignancies, elevated CTLA-4 expression—especially on tumor-infiltrating lymphocytes—often correlates with an immunosuppressive, exhausted T-cell phenotype and poorer prognosis. However, this same expression also marks tumors that may respond to CTLA-4 blockade therapies, highlighting its dual role as a prognostic biomarker and a therapeutic target in the rapidly evolving field of cancer immunotherapy.<br>
70-	CTNNB1	↑	catenin (cadherin-associated protein), beta 1, 88kDa	CGL-Driver Genes	Oncogene	<b>CTNNB1,</b> which encodes the protein beta-catenin, plays a significant role in the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and adhesion. Mutations in the CTNNB1 gene can lead to the stabilization and accumulation of beta-catenin in the cytoplasm and nucleus, resulting in the activation of Wnt target genes that promote oncogenesis.<br> CTNNB1 mutations are commonly associated with several types of cancer.<br> CTNNB1 (which encodes beta-catenin) is considered an oncogene when it is mutated or dysregulated. Overall, CTNNB1 expression and its mutations are often associated with poor prognosis across various cancer types.<br>
844-	CTR1	↑	Copper Transporter 1			<b>CTR1</b> (Copper Transporter 1) is a protein that plays a crucial role in the transport of copper into cells. Copper is an essential nutrient that is required for various cellular processes, including the regulation of cell growth, differentiation, and survival.<br> CTR1 has been found to be overexpressed in various types of tumors, including breast, lung, colon, and prostate cancer. The overexpression of CTR1 in cancer cells has been linked to increased copper uptake, which can promote tumor growth and progression.<br>
500-	CUL4B	↑	Cullin 4B			<b>CUL4B</b> (Cullin 4B) is a member of the Cullin family of proteins, which are part of the ubiquitin-proteasome system. This system is crucial for regulating protein degradation and maintaining cellular homeostasis. CUL4B specifically plays a role in the ubiquitination process, where it helps tag proteins for degradation, thereby influencing various cellular processes, including cell cycle regulation, DNA repair, and response to stress.<br> Elevated levels of CUL4B have been associated with certain types of cancers, including breast cancer and others, suggesting that it may act as an oncogene in these contexts.<br>
1139-	Cupro	∅	Cuproptosis			<b>Cuproptosis</b> is a recently described form of regulated cell death that is distinct from other types such as apoptosis, necroptosis, and pyroptosis. It is primarily characterized by its direct dependence on copper and its interaction with mitochondrial processes.<br> <br> -Cuproptosis begins with the intracellular accumulation of copper. This free copper binds directly to lipoylated proteins, which are enzymes involved in important mitochondrial metabolic processes such as the tricarboxylic acid (TCA) cycle.<br> -Protein Aggregation: The binding of copper to these lipoylated proteins induces their aggregation. This aggregation disrupts normal protein functions and compromises mitochondrial integrity.<br> <br> Cuproptosis represents a unique form of regulated cell death driven by the accumulation of copper and its consequent interactions with mitochondrial lipoylated proteins.<br>
72-	CXCc	↑	CXC chemokine family	HalifaxProj(inhibit)		<b>(Prev called GRO1 oncogene)(KC) belongs to the CXC</b><br> The chemokine ligand 1 (CXCK1) is a small peptide belonging to the CXC chemokine family that acts as a chemoattractant for several immune cells, especially neutrophils or other non-hematopoietic cells to the site of injury or infection and plays an important role in regulation of immune and inflammatory responses.<br> CXCL1 is increased in ovarian cancer via GRB2-associated binding protein 2-dependent autocrine way, promoting tumour cells proliferation and angiogenesis;<br> Keratinocyte-derived chemokine (KC) belongs to the CXC family and it is homologous to interleukin (IL)-8.<br> The CXC chemokines can be further divided into two main subgroups based on the presence or absence of the ELR (Glu-Leu-Arg) motif:<br> 1. ELR+ CXC Chemokines: These include chemokines such as CXCL1, CXCL2, CXCL3, CXCL5, CXCL6, CXCL7, CXCL8 (IL-8), and CXCL12 (SDF-1). They are primarily involved in promoting angiogenesis, recruiting neutrophils, and facilitating tumor growth.<br> 2. ELR- CXC Chemokines: This subgroup includes chemokines like CXCL4, CXCL9, CXCL10, and CXCL11. These chemokines are often associated with anti-tumor immunity and can attract T cells and other immune cells to the tumor microenvironment.<br> CXC chemokines, particularly the ELR+ subset, can promote tumor growth by enhancing angiogenesis. CXC chemokines are involved in the metastatic spread of cancer cells. For example, CXCL12 and its receptor CXCR4 are known to play significant roles in the migration of cancer cells to distant sites, such as the bone marrow and lymph nodes.<br> Given their roles in cancer progression, CXC chemokines and their receptors are being investigated as potential therapeutic targets. <br>
907-	CXCL1	↑	CXCL1			<b>CXCL1</b> is a chemokine that plays a crucial role in the recruitment of immune cells to sites of inflammation and injury. In cancer, CXCL1 has been shown to be overexpressed in various types of tumors.<br>
1247-	CXCL12	↑	SDF–1			<b>SDF–1,</b> also known as CXCL12, is a chemokine with key roles in cell signaling, migration, angiogenesis, and the regulation of the tumor microenvironment. <br> <br> -SDF–1 is widely recognized for its role in tumor progression and metastasis. In many cancers—including breast, colorectal, lung, liver, and pancreatic cancers—increased expression of SDF–1 or hyperactivation of its receptor-mediated signaling is associated with more aggressive disease features and poorer patient outcomes.<br>
1093-	CXCL9	↑	CXCL9			<b>CXCL9</b> (also known as monokine induced by gamma interferon, MIG) is a chemokine that plays a critical role in immune surveillance by recruiting activated T cells, natural killer (NK) cells, and other leukocytes to the tumor microenvironment. Its expression is often regulated by interferon‐γ (IFN-γ) and other inflammatory cytokines. <br> – CXCL9 is often expressed by both tumor and stromal cells.<br> – High expression can be found in tumor microenvironments.<br> – Elevated CXCL9 expression is generally linked to a favorable prognosis due to effective immune cell recruitment.<br> <br> Strategies that boost CXCL9 expression or restore its activity in immunologically "cold" tumors are being explored as potential means to enhance the efficacy of immunotherapies.<br>
921-	CXCR2	↑	CXCR2		chemokine receptor	<b>CXCR2</b> is a chemokine receptor that plays a crucial role in the progression and metastasis of various types of cancer. <br> CXCR2 is often over expression and is associated with poor prognosis and increased risk of metastasis.<br> Several CXCR2 inhibitors, such as SB225002 and AZD5069, have been developed and are being evaluated in preclinical and clinical studies for their potential to treat various types of cancer.<br>
79-	CXCR4	↑	Chemokine Receptor Type 4			<b>Chemokine Receptor Type 4 (CXCR4)</b> is a G protein-coupled receptor that plays a significant role in various physiological processes, including immune responses, hematopoiesis, and organ development. It is also implicated in cancer biology, where it has been associated with tumor progression, metastasis, and the tumor microenvironment.<br> CXCR4 is often overexpressed in various types of cancers, including breast, lung, prostate, and pancreatic cancers. Its activation can promote tumor cell proliferation and survival.<br>
374-	Cyc	?	Cyclin			<b>Cyclins</b> are indispensable elements of the cell cycle and derangement of their function can lead to cancer formation.<br>
653-	cycA1	↑	cyclin A1			<b>Cyclin A1</b> is a protein that plays a crucial role in the regulation of the cell cycle, which is the process by which cells grow and divide. It is overexpressed in various types of cancer, including breast, ovarian, and colorectal cancer, and its overexpression has been linked to poor prognosis and reduced survival rates.<br>
379-	CycB	↑	Cyclin B			<b>When cyclin B levels</b> are elevated, cells can enter M phase prematurely and strict control over cell division is lost, which is favorable for cancer development.<br> Cyclin B is a regulatory protein that plays a crucial role in cell cycle progression, particularly in the transition from the G2 phase to mitosis. Its expression levels can significantly impact cancer progression and patient prognosis.<br> Cyclin B expression is often elevated in various cancers and is generally associated with poor prognosis.<br>
73-	cycD1	↑	cyclin D1 pathway			<b>Also called CCND1</b><br> The main function of cyclin D1 is to maintain cell cycle and to promote cell proliferation. Cyclin D1 is a key regulatory protein involved in the cell cycle, particularly in the transition from the G1 phase to the S phase. It is part of the cyclin-dependent kinase (CDK) complex, where it binds to CDK4 or CDK6 to promote cell cycle progression. <br> Cyclin D1 is crucial for the regulation of the cell cycle. Overexpression or dysregulation of cyclin D1 can lead to uncontrolled cell proliferation, a hallmark of cancer.<br> Cyclin D1 is often found to be overexpressed in various cancers.<br> Cyclin D1 can interact with tumor suppressor proteins, such as retinoblastoma (Rb). When cyclin D1 is overexpressed, it can lead to the phosphorylation and inactivation of Rb, releasing E2F transcription factors that promote the expression of genes required for DNA synthesis and cell cycle progression.<br> Cyclin D1 is influenced by various signaling pathways, including the PI3K/Akt and MAPK pathways, which are often activated in cancer.<br> In some cancers, high levels of cyclin D1 expression have been associated with poor prognosis, making it a potential biomarker for cancer progression and treatment response.<br>
893-	CycD3	↑	Cyclin D3			<b>Cyclin D3</b> is a protein that plays a crucial role in the regulation of cell cycle progression. It is a member of the cyclin family of proteins, which are involved in the regulation of the cell cycle.<br> Cyclin D3 has been found to be overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer.<br> Cyclin D3 has been shown to be involved in the regulation of cancer cell proliferation, and its overexpression has been linked to increased cell growth and survival.<br>
378-	cycE	↑	Cyclin E			<b>Cyclin E</b> regulates multiple downstream molecules, such as the retinoblastoma susceptibility gene (RB1) and the transcription factor E2F.<br> Cyclin E is a prognostic marker in breast cancer, its altered expression increased with the increasing stage and grade of the tumor.<br> Cyclin E is a regulatory protein that plays a critical role in the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression levels can significantly influence cancer progression and patient prognosis. <br> <br> Cyclin E expression is frequently elevated in various cancers and is generally associated with poor prognosis. Its role in promoting cell cycle progression makes it a potential biomarker for tumor aggressiveness and patient outcomes. <br>
725-	cycE1	↑	cyclin E1		protein	<b>Cyclin E1</b> is a protein that plays a crucial role in the regulation of the cell cycle, particularly during the G1 phase. It is a member of the cyclin family, which are proteins that bind to and activate cyclin-dependent kinases (CDKs). The cyclin E1-CDK2 complex is essential for the progression of cells from the G1 phase to the S phase, where DNA replication occurs.<br> <br> In cancer, cyclin E1 has been found to be overexpressed in various types of tumors, including breast, ovarian, and lung cancers. This overexpression can lead to uncontrolled cell proliferation, a hallmark of cancer.<br>
495-	cycF	↑	CCNF cyclin F			<b>Also CCNF</b><br> Cyclin F is a member of the cyclin family that plays a role in regulating the cell cycle, particularly in the transition from the G1 phase to the S phase. Its expression and function can vary across different cancer types, and it has been implicated in cancer progression and prognosis.<br> <br> Cyclin F is often overexpressed in cancer.<br> High Cyclin F levels may correlate with poor prognosis and aggressive tumor behavior.<br>
1314-	CYFRA21-1	↑	cytokeratin 19 fragments			<b>CYFRA 21-1 (cytokeratin 19 fragments) </b><br> CYFRA 21-1 is used primarily as a serum biomarker, especially in lung cancer, and its levels have been correlated with disease stage, treatment response, and overall patient outcomes.<br> <br> • Elevated serum levels have been associated with advanced disease, increased tumor burden, and poorer overall survival in multiple studies.<br>
74-	CYLD	↓	cylindromatosis (turban tumor syndrome)	CGL-Driver Genes	TSG	<b>CYLD (Cylindromatosis)</b> is a gene that encodes a deubiquitinating enzyme, which plays a crucial role in various cellular processes, including the regulation of cell signaling pathways. Mutations in the CYLD gene are associated with several types of cancer, particularly those related to skin and other epithelial tissues.<br> Research has also indicated that CYLD may play a role in other cancers, including breast cancer and colorectal cancer. The exact mechanisms by which CYLD mutations contribute to these cancers are still being studied, but they may involve dysregulation of signaling pathways such as NF-κB and Wnt.<br> CYLD is primarily known as a tumor suppressor gene. Its protein product functions to remove ubiquitin from target proteins, thereby regulating various signaling pathways, including those involved in cell proliferation, apoptosis, and inflammation. Loss of CYLD function can lead to uncontrolled cell growth and tumorigenesis.<br>
454-	CYP11A1	↑	CYP11A1			<b>CYP11A1:</b> gene that encodes a cytochrome P450 enzyme that catalyzes the conversion of cholesterol to pregnenolone, a precursor of steroid hormones.<br> <br> Elevated CYP11A1 levels have been observed in cancer, and its expression may correlate with tumor aggressiveness and patient survival.<br>
449-	CYP17A1	↑	cytochrome P450 CYP17A1			<b>Cytochrome P450 17A1</b> is an enzyme of the hydroxylase type that in humans is encoded by the CYP17A1 gene on chromosome 10.<br> CYP17A1 is critically important in the treatment of castration resistant prostate cancer, for which the CYP17A1 inhibitor abiraterone has proven a highly effective drug. However, CYP17A1 inhibition is also being investigated for the treatment of breast cancer.<br> <br> Elevated CYP17A1 levels have been observed in cancer, and its expression may correlate with tumor aggressiveness and patient survival.<br>
75-	CYP19	↑	CYP19, also known as aromatase			<b>CYP19,</b> also known as aromatase, is an enzyme that plays a crucial role in the biosynthesis of estrogens by converting androgens (such as testosterone and androstenedione) into estrogens (such as estradiol and estrone). The activity of CYP19 is significant in various tissues, including the ovaries, testes, adipose tissue, and the brain.<br> <br> -Estrogen Production: Elevated levels of estrogens, which can result from increased CYP19 activity, are associated with the development and progression of certain cancers, particularly estrogen receptor--positive breast cancer.<br> -Aromatase Inhibitors: In the treatment of hormone-sensitive breast cancer, aromatase inhibitors (such as anastrozole, letrozole, and exemestane) are commonly used. These drugs work by inhibiting the activity of CYP19, thereby reducing estrogen levels and slowing the growth of estrogen-dependent tumors.<br>
76-	CYP1A1	↑	Cytochrome P450 1A1			<b>CYP1A1 (Cytochrome P450 1A1)</b> is an enzyme that plays a significant role in the metabolism of various substances, including drugs, environmental pollutants, and procarcinogens. It is part of the cytochrome P450 family of enzymes, which are involved in the oxidative metabolism of a wide range of compounds.<br> <br> Role in Cancer<br> Activation of Procarcinogens: CYP1A1 is known to convert certain procarcinogenic compounds, such as polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke and grilled meats, into their active forms. These metabolites can bind to DNA and form adducts, leading CYP1A1 expression is a significant factor in the context of various cancers, particularly those associated with environmental and lifestyle factors. to mutations and potentially initiating cancer.<br>
1129-	CYP1A2	?	CYP1A2			<b>CYP1A2, cytochrome P450 enzyme</b><br> – CYP1A2 contributes to the metabolism of xenobiotics and can bioactivate pro-carcinogens into DNA-damaging compounds.<br>
1112-	CYP27B1	↓	CYP27B1			<b>CYP27B1</b> is the enzyme responsible for converting 25‐hydroxyvitamin D into its active form, 1,25‐dihydroxyvitamin D (calcitriol).<br> <br> -A higher expression of CYP27B1 may correlate with a more differentiated tumor phenotype and has been associated in some reports with a better prognosis, potentially via local production of calcitriol that can help regulate cell proliferation and promote apoptosis.<br> - Reduced expression of CYP27B1 has been linked in some cases to more advanced disease and poorer outcomes.<br>
1267-	CYP2C6	?	CYP2C6			<b>CYP2C6</b> belongs to the cytochrome P450 family of enzymes, which are primarily involved in the metabolism of both endogenous and exogenous compounds—including drugs and potential carcinogens.<br> <br> -More than 95% of drugs and natural products are metabolized by CYPs, of which CYP1A, CYP2C, CYP2D, and CYP3A are the most important.<br>
1130-	CYP2C9	?	CYP2C9			<b>CYP2C9, cytochrome P450 enzyme</b><br> – CYP2C9 is involved in the metabolism of a range of xenobiotics, including several anticancer drugs, which can affect drug efficacy and toxicity.<br> – Although CYP2C9 is not traditionally considered an oncogene or tumor suppressor, its expression and genetic variants can influence patient responses to chemotherapy.<br>
1268-	CYP2D1	?	CYP2D1			<b>CYP2D1</b> is a member of the cytochrome P450 enzyme family, but it is less well characterized in human cancer contexts compared to some of its counterparts (such as CYP2D6).<br>
1040-	CYP2E1	↑	cytochrome P450 2E1 (CYP2E1)			<b>CYP2E1</b> is an enzyme belonging to the cytochrome P450 family that is primarily involved in the metabolism of small organic molecules, including drugs, toxins, and endogenous substrates. It plays a significant role in the biotransformation of various compounds through oxidation reactions.<br> <br> Due to its role in metabolizing procarcinogenic compounds, elevated CYP2E1 activity has been linked to an increased risk of certain cancers, particularly in the context of chronic alcohol consumption or exposure to environmental toxins. In some studies, higher CYP2E1 levels have been associated with liver cancer and may also influence risk in other tissues.<br>
1269-	CYP3A2	?	CYP3A2			<b>CYP3A2</b> is part of the CYP3A enzyme subfamily, which is well known for its role in metabolizing a broad range of substrates, including drugs and potentially carcinogenic compounds.<br>
1131-	CYP3A4	↑	CYP3A4			<b>CYP3A4</b> is the most abundant cytochrome P450 enzyme in the liver and is also expressed in extrahepatic tissues.<br> – It metabolizes a wide range of drugs and endogenous substrates, including hormones.<br> <br> – In some studies, higher CYP3A4 expression has been correlated with poorer response to treatment and potentially worse survival.<br>
77-	Cyt‑c	↓	cyt-c Release into Cytosol			<b>Cytochrome c</b><br> ** The term "release of cytochrome c" ** an increase in level for the cytosol.<br> Small hemeprotein found loosely associated with the inner membrane of the mitochondrion where it plays a critical role in cellular respiration. Cytochrome c is highly water-soluble, unlike other cytochromes. It is capable of undergoing oxidation and reduction as its iron atom converts between the ferrous and ferric forms, but does not bind oxygen. It also plays a major role in cell apoptosis. <br> <br> The term "release of cytochrome c" refers to a critical step in the process of programmed cell death, also known as apoptosis.<br> In its new location—the cytosol—cytochrome c participates in the apoptotic signaling pathway by helping to form the apoptosome, which activates caspases that execute cell death.<br> Cytochrome c is a small protein normally located in the mitochondrial intermembrane space. Its primary role in healthy cells is to participate in the electron transport chain, a process that helps produce energy (ATP) through oxidative phosphorylation.<br> Mitochondrial outer membrane permeability leads to the release of cytochrome c from the mitochondria into the cytosol.<br> The release of cytochrome c is a pivotal event in apoptosis where cytochrome c moves from the mitochondria to the cytosol, initiating a chain reaction that leads to programmed cell death.<br> <br> On the one hand, cytochrome c can promote cancer cell survival and proliferation by regulating the activity of various signaling pathways, such as the PI3K/AKT pathway. This can lead to increased cell growth and resistance to apoptosis, which are hallmarks of cancer.<br> On the other hand, cytochrome c can also induce apoptosis in cancer cells by interacting with other proteins, such as Apaf-1 and caspase-9. This can lead to the activation of the intrinsic apoptotic pathway, which can result in the death of cancer cells.<br> Overexpressed in Breast, Lung, Colon, and Prostrate.<br> Underexpressed in Ovarian, and Pancreatic.<br>
1233-	cytoP	?	cytoprotection			<b>The process</b> by which various compounds protect cells from damage.<br>
78-	cytoP450	↑	cytochrome P450 (CYP)			<b>Cytochrome P450 (CYP)</b> enzymes are a large family of enzymes that play a crucial role in the metabolism of various substances, including drugs, environmental chemicals, and endogenous compounds. They are primarily found in the liver but are also present in other tissues. <br> Tumor Microenvironment: CYP enzymes can also be expressed in tumor tissues, where they may contribute to the local metabolism of drugs and other compounds, potentially affecting tumor growth and response to therapy.<br> Some CYPs may be upregulated, while others may be downregulated.<br> CYP1B1 is often overexpressed in breast, prostate, and lung cancers. This overexpression can contribute to the activation of procarcinogens and the metabolism of therapeutic agents, potentially influencing tumor growth and response to treatment.<br> CYP19A1 (aromatase) converts androgens to estrogens, and its expression can be associated with breast cancer progression.<br> <br> Specific CYP enzymes, such as CYP1A1, CYP1B1, CYP17A1, and CYP19A1, have been associated with tumor progression and poor outcomes in various cancers.<br>
80-	DAXX	↓	death-domain associated protein	CGL-Driver Genes	TSG	<b>Death-domain</b> associated proteins are a group of proteins that play crucial roles in the regulation of apoptosis (programmed cell death) and other cellular processes. <br> -Apoptosis Regulation: Proteins with death domains, such as Fas (CD95) and its ligand (FasL), play essential roles in the extrinsic pathway of apoptosis. Dysregulation of these pathways can lead to cancer cell survival.<br> Generally, lower levels of DAXX or mutations in the DAXX gene are associated with poorer outcomes and increased tumor aggressiveness. <br>
572-	DCells	↓	dendritic Cells			<b>Dendritic cells (DCs)</b> are central regulators of the adaptive immune response, and as such are necessary for T cell-mediated cancer immunity.<br> DC subsets are often classified by developmental origin as conventional DC [including type 1 conventional DC (cDC1) and type 2 conventional DC (cDC2)], monocyte-derived DC (MoDC), plasmacytoid DC (pDC) as well as the emerging appreciation of a population, termed DC3.<br> <br> Dendritic cells play a vital role in the immune response to cancer, and their presence and functional status in the tumor microenvironment can significantly impact prognosis. Generally, a higher density of activated dendritic cells is associated with better clinical outcomes across various cancer types.<br>
81-	Dcr	↑	Disturbed circadian rhythms	HalifaxProj(normalize)		<b>Disturbed circadian rhythms</b> have been linked to various health issues, including an increased risk of cancer. The circadian rhythm is the body's internal clock that regulates the sleep-wake cycle and other physiological processes over a 24-hour period.<br> Disturbed circadian rhythms are increasingly recognized as a factor that can influence cancer risk, progression, and prognosis across various cancer types. Disruptions in the natural circadian cycle can lead to alterations in hormone levels, immune function, and cellular processes, potentially contributing to tumor development and aggressiveness.<br>
1092-	decorin	↓	decorin			<b>Decorin</b> is a small leucine‐rich proteoglycan found in the extracellular matrix that plays a multifaceted role in regulating cell growth, angiogenesis, and collagen fibrillogenesis. Its interaction with growth factors (such as transforming growth factor‐β [TGF‐β]), receptor tyrosine kinases, and other extracellular molecules contributes to its ability to influence tumor cell behavior. Numerous studies have investigated the expression of decorin in various cancers, revealing that its levels can influence prognosis.<br> <br> Decorin is generally downregulated in the tumor microenvironment.<br> – Lower decorin levels have been correlated with desmoplasia and a more fibrotic, aggressive tumor phenotype, suggesting poorer prognosis.<br>
380-	DFF45	?	DNA Fragmentation Factor 45 Gene			<b>DFF45</b> was expressed preferably in low-stage neuroblastoma tumors, and to a lesser degree in high-stage neuroblastomas.<br>
960-	DGAT1	↑	Diacylglycerol O-acyltransferase 1			<b>The DGAT1 gene (Diacylglycerol O-acyltransferase 1)</b> is a key regulator of lipid metabolism, particularly in the synthesis of triglycerides. The DGAT1 gene is overexpressed in various types of cancer.<br> <br> DGAT1 gene is a key regulator of lipid metabolism and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.<br>
760-	DHCR24	⇅	24-Dehydrocholesterol Reductase		gene	<b>DHCR24 (24-Dehydrocholesterol Reductase)</b> is a gene that encodes an enzyme involved in the biosynthesis of cholesterol. DHCR24 is also involved in various cellular processes, including cell proliferation, differentiation, and survival.<br>
457-	DHT	↑	dihydrotestosterone level		male hormone	<b>DHT (dihydrotestosterone)</b> is a type of androgen, a male sex hormone, that stimulates the development of masculine characteristics such as body hair, muscle growth, and a deep voice. People who have prostate cancer usually have an increase in DHT levels.<br>
395-	Diablo	↓	Diablo			<b>Diablo</b> homolog is a mitochondrial protein that in humans is encoded by the DIABLO gene on chromosome 12. DIABLO is also referred to as second mitochondria-derived activator of caspases or SMAC. This protein binds inhibitor of apoptosis proteins, thus freeing caspases to activate apoptosis.<br> SMAC/Diablo is known to be a pro-apoptotic protein and its overexpression has been observed to oppose progression of a variety of tumor types. SMAC/Diablo possesses a new lipid synthesis-related function essential for cancer growth, rendering SMAC/Diablo a promising therapeutic target in cancer. Suggesting that the role of SMAC/Diablo in cancer can be a double-edged sword.<br> <br> High levels of Diablo expression have been associated with increased sensitivity to chemotherapy and better prognosis in some cancers, as it may promote apoptosis in cancer cells. Conversely, low levels of Diablo expression might correlate with resistance to treatment and poorer outcomes.<br>
1235-	Diff	↓	differentiation			<b>Differentiation</b> refers to the process by which cells become specialized in structure and function.<br> -In healthy tissues, cells undergo differentiation to become specialized types (e.g., muscle cells, neurons, blood cells) that perform specific functions. This process is tightly regulated by genetic and epigenetic factors.<br> -In some cases, cells can lose their specialized characteristics, a process known as dedifferentiation. This is often seen in cancer, where tumor cells revert to a more primitive, less differentiated state.<br>
1069-	DJ-1	↑	DJ-1			<b>DJ-1 (also known as PARK7)</b> <br> Elevated levels of DJ-1 have been observed in tumors and are often correlated with more advanced disease stages. Overexpression of DJ-1 may contribute to cell proliferation and invasion, leading to an overall poorer prognosis.<br> <br> – DJ-1 functions as an oxidative stress sensor. Under conditions of increased ROS, DJ-1 undergoes specific oxidative modifications that can alter its structure and function. This allows DJ-1 to participate in protective responses against ROS-induced cellular damage. DJ-1 indirectly reduces the generation of excessive ROS and the resulting oxidative damage.<br> -In the context of cancer, increased DJ-1 expression can help tumor cells evade the detrimental effects of ROS, contributing to resistance against oxidative stress–inducing therapies.<br>
652-	DLC1	↓	deleted in liver cancer 1		tumor suppressor gene	<b>DLC1,</b> or deleted in liver cancer 1, is a tumor suppressor gene that is frequently lost or mutated in HCC.<br> DLC1 is a gene that encodes a protein called Rho GTPase-activating protein 54 (RhoGAP54), which plays a role in regulating cell growth and division.<br> <br> DLC1 has been correlated with poor prognosis. Low levels of DLC1 expression are often associated with increased tumor size, higher rates of metastasis, and shorter overall survival rates. Conversely, higher expression levels of DLC1 may indicate a better prognosis and could be linked to a more favorable response to treatment.<br>
1261-	DLEU1	↑	Deleted in Lymphocytic Leukemia 1		oncogenic lncRNA	<b>DLEU1 (Deleted in Lymphocytic Leukemia 1)</b> <br> -In many studies, higher levels of DLEU1 expression have been associated with increased tumor aggressiveness and poorer clinical outcomes.<br>
399-	DNA-PK	↑	DNA-dependent protein kinase			<b>DNA-dependent protein kinase catalytic subunit (DNA-PK)</b> is a pleiotropic kinase involved in DNA repair and transcriptional regulation. DNA-PK is deregulated in selected cancer types and is strongly associated with poor outcome.<br> <br> Elevated levels of DNA-PK have been observed in various cancers, including breast cancer, lung cancer, and liver cancer. High expression levels are often associated with aggressive tumor characteristics and poor prognosis.<br> Conversely, low expression of DNA-PK may be linked to increased sensitivity to certain therapies, particularly those that induce DNA damage, such as radiation and some chemotherapeutic agents.<br>
82-	DNAdam	↑	DNA damage	HalifaxProj(prevent)		<b>DNA damage</b> plays a crucial role in the development of cancer. The integrity of DNA is essential for the proper functioning of cells, and when DNA is damaged, it can lead to mutations that may contribute to cancer progression.<br>
83-	DNAdamC	?	DNA damage control	CGL-GM		<b>Inactivating mutations</b> of the tumor suppressor genes BRCA1 or BRCA2 lead to activation of downstream pathways required to repair DNA damage in the absence of BRCA function. Thus, cancer cells with defects in BRCA1 or BRCA2 are more susceptible to DNA damaging agents or to drugs that inhibit enzymes that facilitate the repair of DNA damage such as PARP [poly(adenosine diphosphate–ribose) polymerase] (136). PARP inhibitors have shown encouraging results in clinical trials when used in patients whose tumors have inactivating mutations of BRCA genes (137). <br> Incapacitate genes like TP53, which would normally respond to DNA damage by triggering cell death.<br>
84-	DNArepair	?	DNA repair	HalifaxProj(enhance)		<b>DNA repair</b> is a crucial cellular process that maintains the integrity of the genome by correcting damage that can occur due to various factors, including environmental stress, radiation, and normal metabolic activities. <br> Radiation and Chemotherapy: These treatments often work by inducing DNA damage, and cancer cells with defective repair mechanisms may be more susceptible to these therapies.<br>
85-	DNMT1	↑	DNA (cytosine-5-)-methyltransferase 1	CGL-Driver Genes	Oncogene	<b>DNMT1</b> overexpression in various cancer types.<br> DNA (cytosine-5-)-methyltransferase 1, commonly referred to as DNMT1, is an enzyme that plays a crucial role in the maintenance of DNA methylation patterns.<br> Increased DNMT1 activity can promote tumorigenesis by facilitating the accumulation of methylation changes that drive cancer progression.<br> Is frequently overexpressed in a variety of cancers, including breast, colorectal, lung, prostate, and hematological malignancies. This overexpression is often associated with hypermethylation of tumor suppressor genes, leading to their silencing and contributing to tumorigenesis.<br>
86-	DNMT3A	↑	DNA (cytosine-5-)-methyltransferase 3 alpha	CGL-Driver Genes	Oncogene	<b>DNA (cytosine-5-)-methyltransferase 3 alpha,</b> commonly referred to as DNMT3A, is an enzyme that plays a crucial role in the process of DNA methylation, which is an important mechanism for regulating gene expression and maintaining genomic stability.<br> The expression levels of DNMT3A and the presence of mutations can serve as prognostic markers in certain cancers. <br> In some cancers, DNMT3A is overexpressed, leading to increased DNA methylation of tumor suppressor genes.<br>
469-	DNMTs	↑	DNA methyltransferase			<b>DNA methylation,</b> an epigenetic modification, regulates gene transcription and maintains genome stability. DNA methyltransferase (DNMT) inhibitors can activate silenced genes at low doses and cause cytotoxicity at high doses.<br> <br> High expression levels of DNMTs, particularly DNMT1 and DNMT3A, are often associated with poor prognosis in several cancers. This is due to their role in promoting tumor growth, metastasis, and resistance to therapies.<br>
1114-	Dose	∅	Dosage			<b>Drug dosage vs efficacy,</b> and actual dosage number of research papers.<br>
87-	DPPH	?	2,2-diphenyl-1-picrylhydrazyl			<b>DPPH (2,2-diphenyl-1-picrylhydrazyl)</b> is a stable free radical commonly used in scientific research to evaluate the antioxidant capacity of various compounds. The DPPH assay is a popular method for assessing the ability of antioxidants to scavenge free radicals, which can contribute to oxidative stress and are implicated in various diseases, including cancer.<br> DPPH itself is not directly related to cancer, its use in assessing antioxidant activity is significant in cancer research.<br> <br> Higher antioxidant activity (as measured by DPPH) may correlate with better outcomes in certain cancers, while in other contexts, it may be associated with tumor aggressiveness.<br>
806-	DR4	↓	Death Receptor 4		protein	<b>DR4 (Death Receptor 4, also known as TRAIL receptor 1 or TNFRSF10A).</b><br> DR4 is one of the main receptors for TRAIL (TNF-related apoptosis-inducing ligand). • Upon TRAIL binding, DR4 can trigger the extrinsic apoptotic pathway, leading to caspase activation and programmed cell death.<br> <br> Lower receptor levels often correlate with therapy resistance and aggressive tumor phenotypes, while appropriate or higher levels may enhance susceptibility to apoptosis-based therapies.<br>
88-	DR5	↑	Death receptor 5			<b>A protein</b> reported to play an important role in sensitizing cancer cells to apoptosis. Death Receptor 5 (DR5), also known as TRAIL receptor 2, is a member of the tumor necrosis factor (TNF) receptor superfamily. It plays a crucial role in the apoptosis (programmed cell death) pathway, particularly in the context of cancer. <br> DR5 is often overexpressed in various types of tumors, including breast, colon, and lung cancers. This overexpression can make cancer cells more susceptible to TRAIL-induced apoptosis.<br>
89-	E-cadherin	↓		HalifaxProj(restore)		<b>Also known as Cadherin1 (CDH1)</b><br> E-cadherin, is a type of cell adhesion molecule that plays a crucial role in maintaining tissue structure and cell-cell interactions. In the context of cancer, E-cadherin has been found to be a tumor suppressor gene.<br> <br> E-cadherin is a transmembrane protein that mediates cell-cell adhesion through its extracellular domain, which interacts with other E-cadherin molecules on adjacent cells. This interaction helps to maintain tissue integrity and prevent cancer cells from invading surrounding tissues.<br> <br> In many types of cancer, including breast, colon, and prostate cancer, E-cadherin expression is often reduced or lost. <br> cell adhesion molecules spanning four families of 1) Integrins (α2β1, α5/β1, αL/β2); 2) Cadherins (E-cad, P-cad, N-cad); 3) Ig-CAMs (VCAM, NCAM, ICAM, Nectins, Necl); and 4) Selectins (E-selectin, P-selectin, L-selectin).<br>
954-	E-sel	↑	E-selectin			<b>E-selectin</b> is a cell adhesion molecule that plays a crucial role in the recruitment of leukocytes to sites of inflammation. In cancer, E-selectin is involved in the interaction between tumor cells and the endothelium, promoting metastasis and tumor progression.<br> <br> E-selectin is expressed on the surface of endothelial cells in tumors, and its expression is associated with increased metastasis and poor prognosis.<br>
90-	E2Fs	↑	E2F family of transcription factors	HalifaxProj(inactivate)		<b>E2Fs</b> have been classified as transcriptional activators (E2F1-3) or transcriptional repressors (E2F4-8), and are thus predicted to play a dual role in human cancers.<br> Activators: E2F1,2,3a,3b<br> Repressors: E2F4,5,6,7a,7b,8<br> As a tumor suppressor and oncogene, the transcription factor E2F1 is a downstream regulator of the Rb pathway.<br> The role of E2Fs in CSCs is widely regarded as an activator gene. Up-regulation of E2Fs is reported to be involved in proliferation promotion (21), maintenance and acquisition of self-renewal (22, 23), invasion and metastatic progression (24) and resistance to chemotherapy and radiotherapy (25) in many CSCs.<br>
841-	E6	↑	E6		oncoprotein	<b>E6</b> is a protein encoded by the human papillomavirus (HPV) genome, specifically by the high-risk HPV types 16 and 18. E6 is a key oncoprotein that plays a crucial role in the development and progression of cervical cancer, as well as other HPV-related cancers.<br> E6 is often used as a biomarker for HPV-related cancers, and its detection can help diagnose and monitor the progression of these cancers.<br>
840-	E7	↑	E7		oncoprotein	<b>E7</b> is a protein encoded by the human papillomavirus (HPV) genome, specifically by the high-risk HPV types 16 and 18. E7 is a key oncoprotein that plays a crucial role in the development and progression of cervical cancer, as well as other HPV-related cancers.<br> E7 is often used as a biomarker for HPV-related cancers, and its detection can help diagnose and monitor the progression of these cancers.<br>
847-	ECAR	↑	Extracellular Acidification Rate			<b>ECAR (Extracellular Acidification Rate)</b> is a measure of the rate at which cells release acidic byproducts, such as lactic acid, into the extracellular environment. In the context of cancer, ECAR is often used as a proxy for glycolytic activity, as cancer cells often exhibit increased glycolysis, even in the presence of oxygen.<br> <br> Studies have shown that cancer cells often have a higher ECAR compared to normal cells, indicating that they are producing more acidic byproducts. This is thought to be due to the fact that cancer cells often rely more heavily on glycolysis for energy production, even in the presence of oxygen.<br>
99-	ECM/TCF	↑	Endothelial cell migration/tip cell formation	HalifaxProj(inhibit)		<b>Endothelial cell migration</b> and tip cell formation are critical processes in angiogenesis, the formation of new blood vessels from pre-existing ones. These processes are particularly relevant in the context of cancer, where tumor growth and metastasis often depend on the development of a robust blood supply.<br> Tumors often secrete pro-angiogenic factors, such as VEGF, to stimulate the formation of new blood vessels. This process allows tumors to obtain the necessary nutrients and oxygen for growth and provides a route for cancer cells to enter the bloodstream and metastasize.<br> Many tumors overexpress VEGF to stimulate angiogenesis, allowing for increased blood supply to support tumor growth. High levels of VEGF are often associated with poor prognosis in various cancers.<br>
91-	EF-1α	↑	elongation factor 1 alpha			<b>Furthermore, overexpression of EF-1α</b> is correlated with increased cell proliferation and oncogenic transformation in breast cancers (20) and is positively associated with prostate cancer progression (21).<br> a protein that plays a crucial role in the process of protein synthesis (translation) in eukaryotic cells. It is involved in the delivery of aminoacyl-tRNA to the ribosome, facilitating the elongation phase of translation.<br> EF-1α is often overexpressed in various types of cancer. This overexpression can contribute to the increased protein synthesis required for rapid cell proliferation and tumor growth.<br>
518-	EFEMP	⇅	EGF-containing fibulin-like extracellular matrix protein			<b>(EFEMP1)</b> has been associated to a variety of malignancies. EFEMP1 can act as both a tumor suppressor and an oncogene. <br> (EFEMP2) has been reported to be related to the progression of various cancers.<br>
961-	eff	∅	efficacy			<b>Power to enhance an anti cancer effect</b>
713-	EGF	?	Epidermal Growth Factor expression			<b>EGF</b> is a protein that acts as a ligand, binding to its receptor, EGFR. It is a potent mitogen, stimulating cell proliferation and differentiation. EGF is involved in various physiological processes, including wound healing, embryonic development, and tissue regeneration. EGF is overexpressed: breast, CRC, GBM, lung, ovarian.<br> EGF is decreased: Prostate, Pancreatic.<br>
94-	EGFR	↑	Epidermal Growth Factor Receptor	HalifaxProj(inhibit) CGL-Driver	Oncogene	<b>EGFR (Epidermal growth factor receptor),</b> which belongs to the tyrosine kinase receptor family (RTKs)<br> Epidermal Growth Factor Receptor (EGFR) is a cell surface protein that plays a crucial role in the regulation of cell growth, survival, proliferation, and differentiation. It is part of the ErbB family of receptors and is activated by binding to its ligands, such as epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-α).<br> <br> -plays a crucial role in regulating cell growth and division.<br> <br> Many cancers exhibit overexpression of EGFR, which can lead to enhanced signaling and contribute to tumor growth and survival. This overexpression is often associated with aggressive tumor behavior and poor prognosis.<br>
1260-	EGR1	⇅	Early Growth Response 1			<b>Early Growth Response 1 (EGR1).</b> EGR1 is an immediate early response transcription factor that regulates genes linked to cell growth, differentiation, apoptosis, and stress responses.<br> <br> - EGR1 rapidly induces or suppresses a broad array of target genes involved in cell cycle control, apoptosis, and cell survival.<br> <br> -Its dualistic nature as both a tumor suppressor and a potential oncogene underscores the importance of context when evaluating its prognostic significance.<br>
40-	EGR4	⇅	Early Growth Response 4			<b>A member of the EGR family,</b> involving in tumorigenesis. EGR4 promoted the proliferation of CRC cells. <br> The expression of EGR4 was abnormally high in 9 cancers and abnormally low in 5 cancers, compared with the corresponding control samples.<br> The prognostic implications of EGR4 expression can vary, with high levels often associated with poor outcomes in some cancers, while in others, it may have protective effects. <br>
509-	eIF2α	?	Eukaryotic translation initiation factor 2			<b>The phosphorylation of eIF2α </b>is carried out by a family of four kinases, PERK (PKR-like ER kinase), PKR (protein kinase double-stranded RNA-dependent), GCN2 (general control non-derepressible-2), and HRI (heme-regulated inhibitor).<br> Eukaryotic translation initiation factor 2 alpha (eIF2α) is a critical protein involved in the initiation of protein synthesis in eukaryotic cells. It plays a key role in regulating translation in response to various cellular stresses, including nutrient deprivation, oxidative stress, and viral infection. The phosphorylation status of eIF2α is particularly important, as it can influence cell survival, apoptosis, and the overall stress response.<br> <br> The phosphorylation status of eIF2α can have significant prognostic implications in cancer. Elevated levels of phosphorylated eIF2α are often associated with poor prognosis in several cancer types, as they may indicate a tumor's ability to adapt to stress and survive in unfavorable conditions.<br>
716-	EIF4E	↑	eukaryotic translation initiation factor 4E		protein	<b>EIF4E:</b> a protein that plays a crucial role in the regulation of protein synthesis, particularly in the translation of mRNAs involved in cell growth, proliferation, and survival. <br> EIF4E overexpressed in: breast, lung, colon, and prostate cancer.<br>
95-	Eifp	↑	Elevated interstitial fluid pressure	HalifaxProj(reduce)		<b>Elevated interstitial fluid pressure (IFP)</b> refers to an increase in the pressure of the fluid that exists in the spaces between cells in tissues. <br> <br> In cancer, rapidly growing tumors can compress surrounding tissues and blood vessels, leading to increased IFP. This can create a hostile microenvironment that promotes tumor progression and metastasis.<br>
452-	Elvol3	?	ELOVL fatty acid elongase 3			<b>Members of this family</b> play a role in elongation of long chain fatty acids to provide precursors for synthesis of sphingolipids and ceramides.<br> Elvol3 (Epithelial-Vascular Endothelial Growth Factor) is a member of the ELOVL (elongation of very long chain fatty acids) family, which is involved in the elongation of fatty acids.<br>
671-	EM	↓	epithelial markers		marker	<b>Epithelial markers</b> are molecules commonly expressed by cells of epithelial origin. These markers include proteins such as E-cadherin, cytokeratins, epithelial cell adhesion molecule (EpCAM), and others. In the context of cancer, the expression of epithelial markers not only defines the cellular lineage but also provides insights into tumor differentiation, invasiveness, and the dynamic process of epithelial-to-mesenchymal transition (EMT). EMT is a critical event during which epithelial cells lose their polarity and cell–cell adhesion properties and gain migratory and invasive traits typically associated with mesenchymal cells.<br> <br> Retained expression of epithelial markers generally correlates with lower invasiveness and a better patient prognosis, while a loss is often indicative of tumor aggressiveness and a greater potential for metastasis.<br>
1020-	EMMPRIN	↑	Extracellular Matrix Metalloproteinase Inducer			<b>EMMPRIN (Extracellular Matrix Metalloproteinase Inducer),</b> also known as CD147 or basigin EMMPRIN is a transmembrane glycoprotein that facilitates intercellular communication.<br> It is best known for its role in upregulating matrix metalloproteinases (MMPs), enzymes that degrade the extracellular matrix (ECM). This degradation is a key step in tumor invasion and metastasis.<br> <br> EMMPRIN is overexpressed in a wide range of cancers, including breast, head and neck, lung, liver, and colorectal cancers, among others.<br> Increased EMMPRIN expression is often observed in more aggressive tumor types and is correlated with enhanced invasive capabilities.<br> High EMMPRIN levels are detected not only in tumor cells but also in the surrounding stromal cells, supporting a pro-tumorigenic microenvironment.<br>
96-	EMT	↑	Epithelial-Mesenchymal Transition			<b>Biological process</b> in which epithelial cells lose their cell polarity and cell-cell adhesion properties and gain mesenchymal traits, such as increased motility and invasiveness. This process is pivotal during embryogenesis and wound healing. Hh signaling pathway is able to regulate the EMT. Snail, E-cadherin and N-cadherin, key components of EMT; EMT-related factors, E-cadherin, N-cadherin, vimentin; The hallmark of EMT is the upregulation of N-cadherin followed by the downregulation of E-cadherin.<br> EMT is regulated by various signaling pathways, including TGF-β, Wnt, Notch, and Hedgehog pathways. Transcription factors such as Snail, Slug, Twist, and ZEB play critical roles in repressing epithelial markers (like E-cadherin) and promoting mesenchymal markers (like N-cadherin and vimentin).<br> EMT is associated with increased tumor aggressiveness, enhanced migratory and invasive capabilities, and resistance to apoptosis.<br>
97-	Endoglin	↑	CD105	HalifaxProj(inhibit)		<b>Endoglin,</b> also known as CD105, is a glycoprotein that is primarily expressed on the surface of endothelial cells and is involved in angiogenesis, the process of new blood vessel formation. Elevated levels of endoglin have been associated with poor prognosis in various cancers, including breast, colorectal, and lung cancers. Its expression levels may serve as a biomarker for tumor progression and response to therapy.<br> <br> Many solid tumors such as breast, lung, colon, and pancreatic cancers exhibit high CD105 expression in their peritumoral and intratumoral vasculature. This is often used as a surrogate marker for the extent of angiogenesis.<br> <br> CD105 (endoglin) is a pivotal protein in the regulation of angiogenesis. In cancer, its high expression—especially on the endothelial cells of tumor vasculature—is often associated with increased angiogenic activity, aggressive tumor behavior, and poorer prognosis.<br>
635-	Endon	⇅	endonuclease			<b>Endonucleases</b> are enzymes that play a crucial role in the maintenance of genome stability by cleaving the phosphodiester backbone of DNA. In the context of cancer, endonucleases can have both tumor-suppressing and tumor-promoting effects.<br> <br> 1. APEX1 (Apurinic/Apyrimidinic Endonuclease 1)<br> Cancers: Breast cancer, lung cancer, colorectal cancer Prognosis: High expression is often associated with poor prognosis due to its role in DNA repair and resistance to chemotherapy.<br> 2. FEN1 (Flap Endonuclease 1)<br> Cancers: Breast cancer, prostate cancer, pancreatic cancer<br> Prognosis: Overexpression is linked to increased tumor aggressiveness and poor survival rates.<br> 3. EXO1 (Exonuclease 1)<br> Cancers: Colorectal cancer, ovarian cancer<br> Prognosis: High levels of EXO1 expression can correlate with poor prognosis and increased risk of metastasis.<br> 4. DNase I (Deoxyribonuclease I)<br> Cancers: Various solid tumors<br> Prognosis: Altered expression levels can be indicative of tumor progression and immune evasion. 5. Caspase-3 (an endonuclease involved in apoptosis)<br> Cancers: Various cancers, including leukemia and solid tumors<br> Prognosis: High levels of active caspase-3 are often associated with increased apoptosis and may correlate with better treatment responses.<br> 6. Rad51 (a recombinase with endonuclease activity)<br> Cancers: Breast cancer, ovarian cancer<br> Prognosis: Elevated expression is often linked to resistance to DNA-damaging therapies and poor prognosis.<br> 7. MRE11 (part of the MRN complex)<br> Cancers: Breast cancer, lung cancer<br> Prognosis: Altered expression can indicate defects in DNA repair mechanisms, influencing treatment outcomes.<br> 8. TDP1 (Tyrosyl-DNA Phosphodiesterase 1)<br> Cancers: Glioblastoma, breast cancer<br> Prognosis: High expression levels may be associated with resistance to certain chemotherapeutic agents.<br> 9. UNG (Uracil-DNA Glycosylase)<br> Cancers: Colorectal cancer, lung cancer<br> Prognosis: Its expression can influence the mutation rate and may correlate with tumor aggressiveness.<br> 10. LIG3 (DNA Ligase III)<br> Cancers: Various cancers, including breast and prostate cancer<br> Prognosis: Overexpression may be linked to enhanced DNA repair capabilities, contributing to treatment resistance.<br>
568-	ENO1	↑	α-Enolase			<b>Also known as 2-phospho-D-glycerate hydrolase</b><br> Is a glycolytic enzyme that catalyzes the conversion of 2-phosphoglyceric acid to phosphoenolpyruvic acid during glycolysis.<br> ENO1's glycolytic function deregulates cellular energetic, sustains tumor proliferation, and inhibits cancer cell apoptosis. Moreover, ENO1 evades growth suppressors and helps tumors to avoid immune destruction. Besides, ENO1 “moonlights” on the cell surface and acts as a plasminogen receptor, promoting cancer invasion and metastasis by inducing angiogenesis. Overexpression of ENO1 on a myriad of cancer types together with its localization on the tumor surface makes it a great prognostic and diagnostic cancer biomarker as well as an accessible oncotherapeutic target.<br>
924-	ENO2	↑	Enolase 2			<b>ENO2 (Enolase 2)</b> is an enzyme that plays a crucial role in the glycolytic pathway, which is often upregulated in cancer cells, and related to poor prognosis.<br> ENO2 (Enolase 2) is a cytoplasmic enzyme that plays a crucial role in the glycolytic pathway, as I mentioned earlier. It is a key enzyme in the conversion of 2-phosphoglycerate to enolpyruvate, which is then converted to pyruvate.<br> <br> ENOX2 (Enox2), on the other hand, is a cell surface enzyme that is also known as Cytosolic Enolase 2 or ENO2 variant. ENOX2 is a truncated form of ENO2 that lacks the first 96 amino acids of the full-length ENO2 protein. Despite this difference, ENOX2 retains enolase activity and is also involved in the glycolytic pathway.<br>
820-	eNOS	⇅	endothelial Nitric Oxide Synthase			<b>Endothelial Nitric Oxide Synthase</b> is an enzyme that is constitutively expressed in endothelial cells, which line the blood vessels.<br>
100-	ENOX	↑	enolase	HalifaxProj(inhibit)		<b>ENOX,</b> or enolase, refers to a family of enzymes involved in the glycolytic pathway, which is crucial for energy production in cells. There are several isoforms of enolase, with ENO1 (alpha-enolase) being the most studied in relation to cancer.<br> <br> Research has shown that ENO1 can be overexpressed in various types of cancer, including breast, lung, and colorectal cancers.<br>
822-	ENOX2	↑	NADH oxidases		"cancer-specific" cell surface marker	<b>NADH oxidases (often referred to as tNOX/ENOX2) </b><br> tNOX stands for "tumor-associated NADH oxidase," and it is also known as ENOX2.<br> ENOX2 (Ecto-Nicotinamide Adenine Dinucleotide Oxidase Disulfide-Thiol Exchanger 2) is a protein that has drawn attention in the context of cancer.<br> ENOX2 is an enzyme found on the cell surface that exhibits NADH oxidase activity along with protein disulfide-thiol interchange activity.<br> Several studies have suggested that ENOX2 could be used as a biomarker for cancer diagnosis, prognosis, and monitoring.<br> <br> NADH oxidases (often referred to as tNOX/ENOX2) and NADPH oxidase family members that have been implicated in redox regulation—detailing their expression in various cancers as well as correlations with prognosis.<br> <br> – tNOX (also known as ENOX2) is a cancer‐specific cell surface NADH oxidase with a role in cellular growth regulation.<br> – This enzyme cycles between hydroquinone oxidase and protein disulfide-thiol interchange activities and is generally not expressed in normal cells.<br> <br> • Expression in Cancer & Prognosis:<br> – ENOX2 is overexpressed in many solid tumors, including breast, prostate, lung, colon, and various hematologic malignancies.<br> – Elevated ENOX2 levels in patient sera or tumor samples have been correlated with aggressive tumor behavior and poor prognosis.<br> – The presence of ENOX2 activity often indicates an increased rate of cell proliferation and may predict recurrence after treatment.<br> <br> ENOX2 is specifically expressed on the cell surface of many cancer cells and is involved in redox regulation and the control of cellular growth.<br> Because ENOX2 is predominantly expressed in tumors rather than normal tissues, it has been explored as a potential diagnostic and prognostic biomarker in oncology.<br> <br> ENOX2 is frequently upregulated or more active in cancer cells.<br> By influencing the balance between NADH and NAD⁺, ENOX2 might shift the cellular redox state. An imbalance can lead to increased oxidative stress or changes in ROS signaling pathways.<br> <br> Potential Effects of Inhibition (**** ROS increase ****)<br> When ENOX2 is inhibited, its NADH oxidase activity is reduced. This can lead to an altered cell redox state.<br> Some studies suggest that blocking ENOX2 activity in cancer cells disrupts their normal redox homeostasis. In certain cases, this disruption may result in the accumulation of NADH and/or an alteration in electron flow—conditions that can favor increased ROS production. Increased ROS can lead to oxidative stress that may trigger cell death (e.g., via apoptosis), which is one of the reasons researchers are interested in ENOX2 as a target for cancer therapy. While there is evidence that inhibiting ENOX2 can lead to an increase in ROS—contributing to oxidative stress and potentially cell death—this outcome is not universal.<br>
969-	EP2	↑	Prostaglandin E2 receptor 2			<b>Also known as PTGER2</b><br> EP2 (Prostaglandin E2 receptor 2) is a receptor that plays a role in various cellular processes, including inflammation and cell growth. In cancer, EP2 has been implicated in tumor development and progression.<br> Tumorigenic potential:<br> -promote tumorigenesis by enhancing cell proliferation and survival<br> -Increasing angiogenesis (formation of new blood vessels)<br> -Suppressing apoptosis (programmed cell death)<br> -Promoting invasion and metastasis<br> <br> Expression levels in cancer:<br> Overexpressed in:Colorectal, Breast, Lung, Prostate, and Ovarian cancer (with generally poor prognosis)<br> Underexpressed in:Some types of gastric cancer (correlated with improved overall survival)<br>
101-	EP300	↑	E1A binding protein p300	CGL-Driver Genes	TSG (actually onocogene)	<b>A transcriptional co-activator</b> that plays a crucial role in regulating gene expression, cell growth, and differentiation. It is involved in various cellular processes, including the response to signaling pathways and the regulation of the cell cycle.<br> EP300 functions as a tumor suppressor in some contexts, while in others, it may promote oncogenic processes. Its role can depend on the specific type of cancer and the molecular context.<br> High levels may correlate with poor survival outcomes.<br> EP300 is a critical player in cancer biology, with its expression levels serving as potential biomarkers for prognosis in various cancers. Its role in transcriptional regulation and chromatin remodeling underscores its importance in tumorigenesis and cancer progression.<br>
970-	EP4	↑	Prostaglandin E2 receptor 4			<b>Also known as PTGER4</b><br> EP4 (Prostaglandin E2 receptor 4) is a receptor that plays a role in various cellular processes, including inflammation and cell growth. In cancer, EP4 has been implicated in tumor development and progression.<br> <br> Overexpressed in: Colorectal, Breast, Lung, Prostate, Ovarian, GBM cancers(with poor prognosis).<br> Underexpressed in: Some types of renal cell carcinoma (correlated with improved overall survival).<br> <br> EP4 appears to play a tumorigenic role in various types of cancer, and its expression levels can be used as a prognostic marker to predict patient outcomes.<br>
102-	EpCAM	↑	epithelial Cell Adhesion Molecule			<b>EpCAM (Epithelial Cell Adhesion Molecule)</b> is a cell surface protein that plays a significant role in cell adhesion, proliferation, and differentiation. It is primarily expressed in epithelial tissues and is involved in various cellular processes, including the maintenance of tissue architecture and the regulation of cell signaling.<br> EpCAM is often overexpressed in various types of cancers, including breast, colorectal, prostate, and lung cancers.<br>
398-	EphB4	↑	tyrosine kinase EphB4			<b>Eph receptors</b> and their Eph receptor-interacting (ephrin) ligands together form an important cell communication system with diverse roles.<br> High EPHB4 expression correlates with advanced prostate cancer stage and poor outcome.<br> EphB4 is often upregulated in cancer, and its expression may be linked to tumor progression and poor prognosis.<br>
612-	EPR	↑	enhanced permeability and retention (EPR) effect			<b>Passive accumulation</b> (in cells) is based on the unique architecture of the tumor tissue, where neo-angiogenesis leads to an atypical endothelial layer and to fenestrated vasculature, which together with the impaired lymphatic drainage guides the penetration and accumulation of nano-sized materials within the cancerous tissues.<br> Exploited for drug design in the nanomedicine field.<br>
504-	EpRE/ARE	?	electrophile response element/antioxidant response element			<b>The electrophile response element (EpRE),</b> also called the antioxidant response element (ARE), is involved in the up-regulation of many antioxidant/detoxifying genes.<br> Electrophile response element (EpRE) is essential for regulation of many genes involved in protection against toxic agents.<br>
103-	ER Stress	?	endoplasmic reticulum (ER) stress signaling pathway			<b>Protein expression of ATF,</b> GRP78, and GADD153 which is a hall marker of ER stress.<br> The endoplasmic reticulum (ER) stress signaling pathway plays a crucial role in maintaining cellular homeostasis and responding to various stressors, including those encountered in cancer. When cells experience stress, such as the accumulation of misfolded proteins, they activate a series of signaling pathways collectively known as the unfolded protein response (UPR). The UPR aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if the stress is unresolved, triggering apoptosis.<br> The activation of ER stress pathways can contribute to resistance against chemotherapy and targeted therapies. Cancer cells may utilize the UPR to survive treatment-induced stress, making it challenging to achieve effective therapeutic outcomes.<br>
843-	ER-α36	↑	estrogen receptor alpha (ERα) protein variant			<b>ER-α36</b> is a variant of the estrogen receptor alpha (ERα) protein. It is a truncated form of the full-length ERα protein.<br> ER-α36 is overexpressed in certain types of breast cancer, including triple-negative breast cancer (TNBC) and tamoxifen-resistant breast cancer. ER-α36 has been found to promote cell proliferation, migration, and invasion in breast cancer cells, contributing to tumor progression and metastasis. The expression of ERα is a significant factor in the prognosis of various cancers, particularly in breast and endometrial cancers, where it is a key target for therapy. The relationship between ERα expression and prognosis can vary widely among different cancer types, and ongoing research is essential to fully understand its role in cancer biology and treatment response.<br>
360-	ER(estro)	↑	Estrogen receptor			<b>Estrogen receptor (ER)</b> signaling is a critical regulator of cell proliferation, differentiation, and survival in breast cancer (BC) and other hormone-sensitive cancers.<br> <br> Estrogen receptors, including ERα and ERβ, are often expressed, but the prognosis with the expression varies.<br>
696-	ERCC1	↑	Excision Repair Cross Complementation group 1		protein	<b>ERCC1 (Excision Repair Cross Complementation group 1)</b> is a protein that plays a crucial role in the repair of DNA damage caused by environmental factors, such as ultraviolet light and chemicals. It is involved in the nucleotide excision repair (NER) pathway, which is responsible for removing damaged DNA segments and repairing them.<br> <br> In the context of cancer, ERCC1 has been found to be overexpressed in various types of tumors, including lung, colon, and ovarian cancers.<br>
105-	ERK	↑	ERK signaling			<b>MAPK3 (ERK1)</b><br> ERK proteins are kinases that activate other proteins by adding a phosphate group. An overactivation of these proteins causes the cell cycle to stop.<br> The extracellular signal-regulated kinase (ERK) signaling pathway is a crucial component of the mitogen-activated protein kinase (MAPK) signaling cascade, which plays a significant role in regulating various cellular processes, including proliferation, differentiation, and survival. high levels of phosphorylated ERK (p-ERK) in tumor samples may indicate active ERK signaling and could correlate with aggressive tumor behavior<br> <br> EEk singaling is frequently activated and is often associated with aggressive tumor behavior, treatment resistance, and poor outcomes.<br>
1014-	ERK5	↑	extracellular signal-regulated kinase 5			<b>ERK5 (extracellular signal-regulated kinase 5, also known as MAPK7)</b><br> ERK5 is part of the MAP kinase family and plays roles in cell proliferation, differentiation, survival, and angiogenesis. Its activation can be triggered by growth factors and various stress signals.<br> <br> Elevated ERK5 activity is generally associated with:<br> -Enhanced tumor cell proliferation<br> -Increased metastatic potential<br> -Shorter survival times and poor prognosis in various cancers (particularly breast, lung, and prostate cancers)<br>
98-	ERS	↑	Endoplasmic reticulum stress	HalifaxProj(induce)		<b>Endoplasmic reticulum (ER)</b> stress is a condition that arises when the ER, a cellular organelle responsible for protein folding, lipid synthesis, and calcium storage, becomes overwhelmed by misfolded or unfolded proteins. This stress can trigger a cellular response known as the unfolded protein response (UPR), which aims to restore normal function by enhancing the protein-folding capacity of the ER, degrading misfolded proteins, and, if necessary, initiating apoptosis (programmed cell death).<br> Cancer cells often experience high levels of ER stress due to rapid proliferation, hypoxia, and nutrient deprivation.<br>
937-	ERα	⇅	Estrogen Receptor alpha			<b>ERα (Estrogen Receptor alpha)</b> is a subtype of estrogen receptor that plays a crucial role in the development and progression of various types of cancer. <br> Cancers with high ERα expression (>50%):BC(80%),EC(80%),OC,Uterine sarcoma<br> Cancers with moderate ERα expression (20-50%):CRC, PCa, Vulvar<br> Cancers with low ERα expression (<20%):Lung, PC, GC<br>
515-	ERβ	↓	Estrogen receptor beta also known as NR3A2			<b>ERβ (or NR3A2)</b> one of two main types of estrogen receptor—a nuclear receptor which is activated by the sex hormone estrogen. In humans ERβ is encoded by the ESR2 gene.<br> ERβ is a potent tumor suppressor and plays a crucial role in many cancer types such as prostate cancer and ovarian cancer.<br> Expression levels of the full length ERβ1 isoform are often lower in aggressive cancers as compared to normal tissue. High ERβ1 expression is associated with improved overall survival in women with breast cancer. The promise of ERβ activation, as a potential targeted therapy, is based on concurrent activation of multiple tumor suppressor pathways with few side effects compared to chemotherapy.<br>
106-	Estro	↑	Estrogen			<b>Estrogen</b> is a hormone that plays a crucial role in the development and regulation of the female reproductive system and secondary sexual characteristics. <br> Estrogen can promote the growth of certain types of breast cancer cells. Many breast cancers are hormone receptor-positive, meaning they have receptors for estrogen.<br> Estrogen expression in cancer primarily refers to the presence and activity of estrogen receptors (ER) in various types of tumors, particularly breast and endometrial cancers. <br> There are two main types of estrogen receptors: ERα and ERβ. These receptors are proteins that, when bound by estrogen, can regulate the expression of target genes involved in cell growth, differentiation, and survival.<br> Treatments for ER-positive breast cancer often include selective estrogen receptor modulators (SERMs) like tamoxifen, which block estrogen's effects, and aromatase inhibitors, which reduce estrogen production in the body.<br> Estrogen binds to estrogen receptors (ERα and ERβ), promoting cell proliferation and survival.<br>
107-	EstroRS	↑	Estrogen receptor signaling	HalifaxProj(suppress)		<b>Estrogen receptor (ER)</b> signaling plays a crucial role in various physiological processes, including the regulation of the menstrual cycle, reproductive functions, and bone health. <br> There are two main types of estrogen receptors:<br> <br> ERα (Estrogen Receptor Alpha): Primarily found in breast tissue, it is the most studied receptor in relation to breast cancer.<br> ERβ (Estrogen Receptor Beta): Found in various tissues, including the ovaries, prostate, and brain, its role in cancer is less well understood.<br> Approximately 70% of breast cancers are ER-positive, meaning they grow in response to estrogen. ER signaling promotes cell proliferation and survival, contributing to tumor growth.<br>
108-	EZH2	↑	enhancer of zeste homolog 2 (Drosophila)	CGL-Driver Genes	Oncogene	<b>EZH2 (Enhancer of Zeste Homolog 2)</b> is a gene that encodes a protein which is a key component of the Polycomb Repressive Complex 2 (PRC2). This complex is involved in the regulation of gene expression through histone methylation, specifically the trimethylation of histone H3 at lysine 27 (H3K27me3), which leads to transcriptional repression of target genes.<br> EZH2 is often overexpressed in various types of cancers, including breast, prostate, and lymphoma. This overexpression can lead to the silencing of tumor suppressor genes, contributing to uncontrolled cell proliferation and survival.<br>
565-	F-actin	↑	fibrous actin			<b>A fibrous actin</b> polymerized in the form of a double helix that is produced in the presence of a metal cation (as of calcium) and ATP.<br> Dynamic rearrangements of the F-actin cytoskeleton are a hallmark of tumor metastasis.<br> <br> F-actin plays a significant role in the progression and prognosis of various cancers. Its expression and dynamics are often linked to increased invasiveness, metastatic potential, and treatment resistance. In many cancer types, high levels of F-actin correlate with poor prognosis and aggressive disease. <br>
551-	FABP4	↑	Fatty acid-binding proteins 4			<b>Belongs</b> to a family of intracellular lipid-binding protein, can bind hydrophobic ligands to regulate lipid trafficking and metabolism. <br> Has been found to be upregulated in many malignant solid tumors, and correlated with poor prognosis.<br>
109-	FADD	↑				<b>FADD (Fas-associated protein with death domain)</b> is a protein that plays a crucial role in the apoptotic signaling pathway, particularly in the process of programmed cell death. It is involved in the signaling of death receptors, such as Fas (CD95), which, when activated, can lead to apoptosis in cells.<br> FADD has a dual role. On one hand, it can promote apoptosis in response to certain signals, which is a mechanism that can prevent the proliferation of cancer cells. On the other hand, some cancer cells may exploit the apoptotic pathways to evade cell death, leading to tumor survival and growth.<br> <br> Expression: FADD is often expressed in breast cancer cells, and its levels can vary among different subtypes.<br> Prognosis: High levels of FADD expression have been associated with increased apoptosis in response to certain therapies, which may correlate with better treatment outcomes. However, in some contexts, FADD can also promote cell survival, complicating its role in prognosis.<br>
110-	FAK	↑	FAK signaling	HalifaxProj(inhibit)		<b>FAK (Focal Adhesion Kinase)</b> is a non-receptor tyrosine kinase that plays a crucial role in cellular processes such as adhesion, migration, proliferation, and survival. It is primarily localized at focal adhesions, where it interacts with integrins and other signaling molecules. FAK promotes cell proliferation by activating signaling pathways such as the PI3K/Akt and MAPK/ERK pathways. These pathways are often upregulated in cancer cells, leading to uncontrolled growth.<br>
111-	FAM123B	↑	family with sequence similarity 123B	CGL-Driver Genes	TSG	<b>FAM123B,</b> also known as FAM123B or DAP (differentially expressed in adenocarcinoma of the prostate), is a protein that has been implicated in various cellular processes, including cell adhesion, migration, and signaling pathways. <br> FAM123B may play a role in cellular processes such as cell proliferation, differentiation, and apoptosis, which are critical in the development and progression of cancer.<br> FAM123B expression may contribute to tumorigenesis. For instance, overexpression of FAM123B has been linked to increased cell proliferation and survival.<br> FAM123B expression levels have been found to be altered compared to normal tissues. This can include both upregulation and downregulation, depending on the specific cancer type and context. Sometimes expressed in cancers, with prognosis not well defined.<br>
1074-	FAM72A	↑	FAM72A			<b>FAM72A</b> belongs to the FAM72 gene family.<br> – Early studies suggest a potential role in regulating cell cycle progression and/or DNA repair mechanisms. <br> <br> – Studies examining the expression of FAM72A in various cancers (using both human samples and murine models) have reported that its upregulation may be associated with tumor growth.<br>
1044-	FAO	↑	Fatty Acid Oxidation			<b>FAO (also known as β-oxidation)</b> is a metabolic process in which fatty acids are broken down in the mitochondria (and, to a lesser extent, in peroxisomes) to generate acetyl-CoA. This acetyl-CoA then enters the tricarboxylic acid (TCA) cycle, ultimately driving the production of ATP via oxidative phosphorylation. FAO is crucial for energy production, especially under conditions where carbohydrates are scarce.<br> <br> While many cancer cells are known for their reliance on glycolysis (the Warburg effect), some tumors exploit FAO to meet their energy needs. FAO can provide a high yield of ATP, which is particularly valuable in nutrient-deprived or hypoxic microenvironments. Tumor cells with high FAO activity may use it to sustain survival, promote proliferation, and support metastatic processes.<br> <br> High FAO activity has been correlated with aggressive tumor behavior and poorer prognosis in certain cancers. Enhanced FAO may support survival under metabolic stress and contribute to resistance against treatments that target glycolytic pathways. Thus, tumors with elevated FAO could potentially be more difficult to treat.<br>
1229-	Fap1	↑	PTPN13			<b>Fas-associated phosphatase-1 (Fap-1),</b> also known as PTPN13 (protein tyrosine phosphatase non-receptor type 13).<br> <br> Fap-1 negatively regulates Fas-mediated apoptosis by dephosphorylating or modulating components of the Fas signaling pathway. Overexpression of Fap-1 in tumor cells can result in resistance to apoptosis, potentially contributing to tumor cell survival and resistance to therapy.<br>
112-	Fas	↑	Fas Death receptor			<b>Fas (also known as CD95 or APO-1)</b> and Fas ligand (FasL) are proteins that play a crucial role in the regulation of programmed cell death, also known as apoptosis.<br> <br> The Fas/FasL system is involved in the elimination of damaged or unwanted cells, including cancer cells.<br> Fas agonists, which mimic the action of FasL, have been shown to induce apoptosis in cancer cells. FasL inhibitors, which block the interaction between Fas and FasL, have been shown to enhance the effectiveness of chemotherapy and immunotherapy<br> <br> Fas is often expressed ,and may be associated with better responses to chemotherapy, but its role in promoting cell survival in certain contexts can complicate its prognostic implications.<br>
744-	fascin	↑	fascin		protein	<b>Fascin</b> is a protein that plays a crucial role in the regulation of cell adhesion, migration, and signaling. In the context of cancer, fascin has been found to be overexpressed in various types of tumors, including breast, lung, colon, and esophageal cancers.<br>
593-	FasL	⇅	Fas ligand			<b>Fas ligand (FasL)</b> is a protein that plays a crucial role in the regulation of the immune system and programmed cell death, also known as apoptosis. In the context of cancer, FasL has been found to have both tumor-promoting and tumor-suppressing effects.<br> FasL is upregulated in melanoma, colon.<br> FasL: tumor suppressing effect on Breast and Lung cancer.<br> <br> FasL inhibitors, which block the interaction between Fas and FasL, have been shown to enhance the effectiveness of chemotherapy and immunotherapy<br>
931-	FASN	↑	Fatty acid synthase			<b>Fatty acid synthase (FASN)</b> is an enzyme involved in the synthesis of fatty acids, which are essential for cell growth and proliferation. Overexpression of FASN has been observed in various types of cancer, and it is often associated with poor prognosis.<br> -fatty acid synthase (FAS) has been demonstrated to play an important role in carcinogenesis by protecting cells from apoptosis<br> <br> FASN (fatty acid synthase) is a key enzyme in the de novo synthesis of fatty acids and has been widely studied in cancer due to its role in lipid metabolism and energy production. Altered FASN expression has been reported in various malignancies, and its prognostic implications have been explored across several tumor types. <br> <br> FASN is frequently overexpressed in a variety of cancers, including breast, prostate, colorectal, ovarian, and others.<br> • Many cancers require high levels of fatty acid synthesis for the generation of new membranes and for signaling lipid molecules.<br> • Higher FASN expression is generally associated with more aggressive cancer phenotypes, increased metastatic potential, and poorer patient outcomes.<br> • Its role in promoting de novo fatty acid synthesis links it directly to the metabolic demands of rapidly dividing cancer cells, making it both a prognostic biomarker and a promising therapeutic target.<br>
1058-	FBI-1	↑	FBI‑1 (Pokemon/ZBTB7A)			<b>FBI-1</b> (also known as Pokemon, encoded by the ZBTB7A gene) <br> FBI‑1 is a transcriptional regulator that can act as either a repressor or an activator of target genes.<br> • It is involved in processes such as cell cycle progression, apoptosis, and metabolism.<br> <br> Overexpression of FBI‑1 in tumors such as breast, colorectal, lung, and ovarian cancer has been associated in many reports with more aggressive tumor behavior and potentially poorer prognostic outcomes.<br>
1298-	FBP1	↓	fructose-1,6-bisphosphatase 1			<b>FBP1 (fructose-1,6-bisphosphatase 1)</b> is a key enzyme in gluconeogenesis<br> <br> -Loss of FBP1 (often due to promoter hypermethylation) facilitates a metabolic switch in cancer cells—referred to as the “Warburg effect” (whereby cancer cells preferentially use glycolysis over oxidative phosphorylation even in the presence of oxygen). This supports rapid cell proliferation and survival under stress.<br> -The downregulation of FBP1 may be associated with enhanced tumor growth and poor survival.<br>
946-	FBPase	↓	Fructose-1,6-Bisphosphatase			<b>Fructose-1,6-bisphosphatase (FBPase)</b> is a key enzyme of gluconeogenesis that has garnered significant attention in cancer research. Altered metabolic pathways are hallmarks of cancer, and many tumors rely on aerobic glycolysis (the Warburg effect) rather than oxidative phosphorylation even in the presence of oxygen. In this context, the expression and activity of FBPase—primarily FBP1 and to some extent FBP2—play important roles in modulating cancer metabolism as well as impacting patient prognosis.<br> <br> FBP1 (Fructose-1,6-Bisphosphatase 1) is a key enzyme in gluconeogenesis, the process by which cells generate glucose from non-carbohydrate sources. FBP1 is often downregulated in cancer cells, and its low expression is associated with poor prognosis.<br> FBP1 is a key enzyme in the regulation of the Warburg effect, a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. FBP1 activators are being developed as a potential therapeutic strategy for cancer treatment.<br> <br> Key Role in Gluconeogenesis<br> -FBPase catalyzes the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate, which is a pivotal step in gluconeogenesis.<br> -This counteracts glycolysis—a pathway often upregulated in cancer cells to support rapid proliferation and biomass generation.<br> <br> Altered FBPase Expression in Cancer<br> -A decrease or loss of FBP1 expression has been observed in several cancer types<br> <br> <br> FBP1:<br> -Primarily found in the liver and kidney.<br> -Plays a central role in gluconeogenesis by catalyzing the conversion of fructose-1,6-bisphosphate to fructose-6-phosphate.<br> -Its expression is more frequently linked to altered metabolic states in various cancers (e.g., reduced FBP1 is often associated with a glycolytic and more aggressive tumor metabolism).<br> <br> FBP2:<br> -Known as the muscle isoform of fructose-1,6-bisphosphatase.<br> -While it performs a similar catalytic function, its expression profile and regulation differ from FBP1 and it is less commonly associated with the metabolic rewiring observed in many cancers.<br>
113-	FBXW7	↓	F-box and WD repeat domain containing 7	CGL-Driver Genes	TSG (tumor suppressor gene)	<b>Also known as FBW7.</b><br> FBXW7, a member of the F-box protein family within the ubiquitin–proteasome system, performs an indispensable role in orchestrating cellular processes through ubiquitination and degradation of its substrates, such as c-MYC, mTOR, MCL-1, Notch, and cyclin E. Mainly functioning as a tumor suppressor.<br> FBW7 mutations or loss of function have been observed in solid tumors such as colorectal cancer, breast cancer, and pancreatic cancer. The loss of FBW7 activity can lead to the accumulation of oncogenic proteins like c-Myc, Notch, and cyclin E, which drive tumorigenesis.<br> FBW7 mutations have been associated with several types of cancer, reinforcing its classification as a tumor suppressor gene.<br> <br> FBXW7 is a critical regulator of protein degradation and plays a significant role in the progression and prognosis of various cancers. Its often downreguled or mutated and is often associated with poor prognosis, increased tumor aggressiveness, and resistance to therapies.<br>
804-	Fenton	↑	Fenton Reaction			<b>The Fenton reaction</b> is a chemical reaction that involves the catalytic decomposition of hydrogen peroxide (H2O2) by iron ions (Fe2+ or Fe3+). This reaction produces highly reactive oxygen species (ROS), including hydroxyl radicals (·OH) and superoxide anions (O2·-).<br> Cancer Progression:<br> Increased oxidative stress from the Fenton reaction can promote cancer cell proliferation, survival, and metastasis. ROS can activate various signaling pathways that support tumor growth and resistance to apoptosis.<br> Therapeutic Target:<br> The Fenton reaction has been explored as a potential therapeutic target. Strategies to manipulate iron levels or enhance the production of ROS in cancer cells are being investigated to selectively induce cell death in tumors.<br> <br> Formula <br> Fe2+ + H2O2 → Fe3+ + HO• + OH−<br> Fe3+ + H2O2 → Fe2+ + HOO• + H+<br> 2 H2O2 → HO• + HOO• + H2O net reaction<br> <br> – The dysregulation of iron metabolism in certain cancers might serve as a biomarker for targeted treatments that employ Fenton reaction-based strategies.<br> – Researchers are investigating strategies that harness or amplify the Fenton reaction to selectively kill cancer cells.<br> - With more available iron, the Fenton reaction can be enhanced, resulting in increased production of hydroxyl radicals. Which can lead to cancer cell death.<br> <br> See the ROS target for more information<br>
573-	Ferritin	↑	SF serum Ferritin			<b>It is widely accepted</b> that there is a strong relationship between iron levels and cancer. . Serum ferritin levels are elevated in many malignancies.<br> Gynecological malignant tumor patients with high serum ferritin levels have significantly less survival time than patients with low or normal serum ferritin levels.<br>
114-	Ferroptosis	?			type of cell death	<b>Type of programmed cell death dependent on iron.</b><br> Ferroptosis is a form of regulated cell death characterized by the accumulation of lipid peroxides to lethal levels. It is distinct from other forms of cell death, such as apoptosis, necrosis, and autophagy. The process of ferroptosis is heavily dependent on iron metabolism and reactive oxygen species (ROS).<br> The accumulation of lipid peroxides is a hallmark of ferroptosis. This can occur when the antioxidant defenses, such as glutathione and selenoproteins, are overwhelmed or inhibited. Many cancer cells upregulate GPX4 to evade ferroptosis, making it a potential target for therapy. It has been described that GPX4, xCT and ACSL-4 are the main targets in the regulation of ferroptosis.<br>
362-	FGF	↑	Fibroblast growth factors			<b>Fibroblast growth factors (FGFs)</b> have diverse functions in the regulation of cell proliferation and differentiation in development, tissue maintenance, wound repair, and angiogenesis.<br> <br> FGFs play a significant role in cancer biology, influencing processes such as cell proliferation, survival, and angiogenesis. Their expression is often associated with poor prognosis and increased tumor aggressiveness across various cancer types. Targeting FGF signaling pathways is being explored as a potential therapeutic strategy in cancer treatment. <br>
1279-	FGF21	⇅	FGF21			<b>Fibroblast Growth Factor 21 (FGF21).</b> FGF21 is best known as a metabolic regulator involved in energy homeostasis.<br> <br> – FGF21 is an endocrine member of the fibroblast growth factor family primarily secreted by the liver, but also produced by adipose tissue and skeletal muscle.<br>
1159-	FGFR1	↑	Fibroblast Growth Factor Receptor 1			<b>Fibroblast Growth Factor Receptor 1 (FGFR1)</b> is a transmembrane receptor tyrosine kinase that binds fibroblast growth factors (FGFs) to initiate signaling cascades regulating cell proliferation, differentiation, migration, and survival. Aberrant FGFR1 signaling—caused by gene amplification, mutations, or overexpression—has been linked to various cancers and can influence prognosis.<br> <br> -Abnormal FGFR1 expression (usually overexpression or gene amplification) is observed in a diverse range of cancers, including lung cancer (notably squamous cell carcinoma), breast cancer, and hematologic malignancies, among others.<br> -FGFR1 gene amplification or overexpression often correlates with enhanced mitogenic signaling, contributing to tumor cell proliferation and survival.<br>
115-	FGFR2	↑	fibroblast growth factor receptor 2	CGL-Driver Genes	Oncogene	<b>FGFR2 (Fibroblast Growth Factor Receptor 2)</b> is a receptor that plays a crucial role in various cellular processes, including cell growth, differentiation, and survival. <br> FGFR2 expression is often associated with aggressive disease, poor prognosis, and resistance to conventional therapies.<br>
116-	FGFR3	↑	fibroblast growth factor receptor 3	CGL-Driver Genes	Oncogene	<b>Fibroblast growth factor receptor 3 (FGFR3)</b> is a member of the fibroblast growth factor receptor family, which plays a crucial role in various biological processes, including cell growth, differentiation, and tissue repair. FGFR3 is particularly known for its involvement in bone development and maintenance.<br> FGFR3 has been implicated in several types of tumors, most notably in bladder cancer. Mutations and overexpression of FGFR3 can lead to aberrant signaling pathways that promote tumorigenesis.<br>
654-	Fibronectin	↑	Fibronectin			<b>Fibronectin</b> is a high-molecular weight glycoprotein that plays a crucial role in cell adhesion, migration, and tissue repair. It is a key component of the extracellular matrix (ECM) and is involved in various cellular processes, including cell signaling, differentiation, and survival. Studies have shown that fibronectin is overexpressed in various types of cancer, including breast, lung, colon, and ovarian cancer. High levels of fibronectin have been associated with poor prognosis and reduced survival in cancer patients.<br>
117-	Fibrosis	↑		HalifaxProj(inhibit)		<b>Causes tissue to overgrow,</b> harden, and scar due to chronic inflammation Chronic fibrosis can create an environment conducive to cancer development. For example, in liver cirrhosis (a form of fibrosis), there is an increased risk of liver cancer (hepatocellular carcinoma). Similarly, pulmonary fibrosis has been associated with an increased risk of lung cancer.<br> <br> Fibrosis plays a significant role in cancer biology, influencing tumor progression, metastasis, and treatment response. The fibrotic microenvironment can create conditions that support tumor growth and resistance to therapies, often correlating with poor prognosis across various cancer types.<br>
389-	FKBP5	↑	FK506 binding protein 51			<b>FKBP5</b> shares characteristics with other FKBPs, it also has unique features, especially its role in the regulation of multiple signalling pathways and in tumourigenesis and chemoresistance. Major function of FKBP5 is its involvement in the modulation of steroid receptor function, including progesterone, androgen(AR) and glucocorticoid receptors (GR), by forming a complex with the heat shock proteins Hsp90/Hsp70.<br> <br> FKBP5 is a critical regulator of stress responses and has significant implications in cancer biology. Its expression is often associated with poor prognosis and increased tumor aggressiveness across various cancer types.<br>
347-	FLRT2	?	FLRT2 gene		Gene	<b>FLRT2</b> functions as Tumor Suppressor gene. (down regulated in Breast Cancer).<br> FLRT2, a member of the FLRT family of proteins.<br> The FLRT2 gene (Fibronectin Leucine-Rich Transmembrane Protein 2) is part of a family of genes that encode proteins involved in cell adhesion and signaling.<br> <br> FLRT2 is a protein involved in cell adhesion and signaling, and its expression can be altered in various cancers. While there is some evidence suggesting that FLRT2 may play a role in tumor progression and metastasis, the specific implications for prognosis in different cancer types are still being investigated.<br>
118-	FLT3	↑	fms-related tyrosine kinase 3	CGL-Driver Genes	Oncogene	<b>FMS-related tyrosine kinase 3 (FLT3)</b> is a receptor tyrosine kinase that plays a significant role in hematopoiesis and is primarily expressed in hematopoietic stem cells and progenitor cells. It is particularly important in the context of acute myeloid leukemia (AML), where mutations in the FLT3 gene are among the most common genetic alterations.<br> FLT3 inhibitors, such as midostaurin, gilteritinib, and quizartinib, have been developed to specifically target and inhibit the activity of the mutated FLT3 receptor. <br>
397-	FLT4	↑	Fms-related tyrosine kinase 4			<b>A gene</b> that encodes a protein that is a receptor tyrosine kinase in the vascular endothelial growth factor receptor (VEGF) family.<br> Flt4 has also been shown to be expressed selectively in subsets of cancer cells.<br> FLT4 (Fms-related tyrosine kinase 4), also known as VEGFR-3 (Vascular Endothelial Growth Factor Receptor 3), is primarily involved in lymphangiogenesis and has been studied in various cancers. Its expression can be associated with tumor progression, metastasis, and prognosis in different cancer types.<br> FLT4 over expression is often associated with aggressive tumor behavior and poor prognosis across various cancer types. <br>
1214-	FOSB	↓	FOSB			<b>FOSB—and,</b> more broadly, related AP‐1 family members—in various cancers and their prognostic implications. Keep in mind that:<br> <br> • The AP‐1 complex is composed of Fos (including FOSB, c‐Fos, Fra-1, Fra-2) and Jun family proteins, and the prognostic role of any one component (like FOSB) may be context‐ and cancer‐type–dependent.<br> <br> • In many cases, altered expression (up‐ or down‐regulation) of these proteins has been correlated with tumor progression, metastasis, or response to treatment.<br> <br> -Where lower levels might be associated with poorer prognosis.<br> • Some reports indicate that decreased expression of certain AP‐1 proteins (or an imbalance in the complex subunits, including FOSB) may be linked to advanced tumor stages and a poorer outcome.<br>
1210-	FOSL1	↑	FOSL1 (FRA-1)			<b>FOSL1 (FRA-1)</b><br> FOSL1 is a member of the activator protein-1 (AP-1) transcription factor complex. It is involved in regulating genes that control proliferation, differentiation, survival, and metastasis.<br> <br> – Observations: Overexpression of FOSL1 has been associated with aggressive subtypes, epithelial–mesenchymal transition (EMT), and increased invasiveness.<br> <br> – Prognostic Implication: Higher FOSL1 levels often correlate with poorer overall survival and disease progression.<br>
462-	FOXD3	↓	FOXD3		tumor suppressor	<b>In human cancer tissue,</b> the expression of FOXD3 is reduced.<br> FOXD3 may play a protective role in human colon formation by regulating EGFR/Ras/Raf/MEK/ERK signal pathway.<br>
119-	FOXL2	↑	forkhead box L2	CGL-Driver Genes	Oncogene	<b>FOXL2</b> is particularly important in the development and function of the ovaries and has been implicated in several types of cancer, especially those related to the reproductive system.<br> FOXL2 is often expressed in ovarian tissues, and its dysregulation has been associated with ovarian tumors.<br> FOXL2 expression has also been observed in other malignancies.<br>
351-	Foxm1	↑	FOXM1 transcription factor			<b>FOXM1</b> transcription factor is a regulator of a broad range of biological processes. Elevated and deregulated FOXM1 expression is found in a wide spectrum of cancers. FOXM1 also plays a central role in cancer initiation, progression and anti-cancer drug resistance. FOXM1 is repeatedly overexpressed in a variety of human cancers.<br> High FOXM1 expression is associated with aggressive tumor characteristics and poor overall survival. FOXM1 is generally considered a marker of poor prognosis across various cancer types.<br>
525-	FOXO	↓	Forkhead box O			<b>FOXO (Forkhead box O)</b> refers to a family of transcription factors that play a crucial role in various cellular processes, including cell cycle regulation, apoptosis (programmed cell death), and stress resistance. The FOXO proteins, particularly FOXO1, FOXO3, FOXO4, and FOXO6, are involved in the regulation of genes that control these processes.<br> FOXO proteins can act as tumor suppressors. They promote apoptosis and inhibit cell proliferation, which can help prevent the development and progression of tumors. When FOXO is activated, it can lead to the expression of genes that induce cell cycle arrest and apoptosis, thereby inhibiting cancer cell growth.<br> FOXO proteins are regulated by phosphorylation through pathways such as the PI3K/Akt pathway. When Akt is activated, it phosphorylates FOXO, leading to its exclusion from the nucleus and subsequent degradation.<br>
1164-	FOXO1	↓	Forkhead box O1			<b>FOXO-1</b> contributes to cellular homeostasis by regulating genes involved in apoptosis, cell cycle arrest, and metabolism.<br> <br> – In many cancers, FOXO-1 activity can be reduced via genetic or epigenetic mechanisms, altered subcellular localization (e.g., cytoplasmic sequestration following phosphorylation by Akt), or protein degradation.<br> – This loss of nuclear FOXO-1 activity is often associated with diminished tumor suppressor functions.<br> – Decreased nuclear FOXO-1 expression or activity correlates with higher tumor grade and poorer prognosis.<br> <br> – FOXO-1 is a key downstream target of the PI3K/Akt pathway. Hyperactivation of Akt, common in many cancers, leads to FOXO-1 inactivation.<br>
997-	FOXO3	↓	Forkhead Box O3			<b>FOXO3 (Forkhead Box O3)</b> is a transcription factor that plays a critical role in regulating apoptosis, cell cycle arrest, DNA repair, and cellular stress responses.<br> <br> • Positive Prognostic Marker<br> – In several cancers, higher nuclear FOXO3 expression (denoting active, transcriptionally functional FOXO3) is generally associated with a more favorable prognosis.<br> – Active FOXO3 can promote cell cycle arrest and apoptosis, thereby inhibiting tumor progression.<br> <br> • Negative Prognostic Implications<br> – Conversely, reduced or cytoplasmically sequestered FOXO3 (often due to hyperactivation of the PI3K/Akt signaling pathway) has been linked to aggressive disease and poorer survival<br>  – Loss of FOXO3 function can allow tumor cells to proliferate unchecked and resist apoptosis, which contributes to a worse outcome.<br>
1177-	FOXO4	↓	Forkhead box O 4			<b>FOXO4</b> is a member of the Forkhead box O (FOXO) family of transcription factors that play key roles in regulating numerous cellular processes, including cell cycle progression, apoptosis, DNA repair, oxidative stress resistance, and cellular senescence.<br> -Under normal conditions, FOXO4 contributes to tumor suppression by inducing cell cycle arrest and apoptosis, thereby limiting malignant transformation.<br> -Its activity is often inhibited in various cancers, either through post-translational modifications (e.g., phosphorylation by oncogenic kinases such as AKT) or altered expression, which can contribute to cancer progression.<br>
581-	FOXP3	↑	forkhead box P3		TSG (not)	<b>Also known as scurfin</b><br> Forkhead box P3 (FOXP3), an X-linked tumor suppressor gene.<br> appears to function as a master regulator of the regulatory pathway in the development and function of regulatory T cells.<br> FOXP3 can promote the apoptosis of breast cancer cells by upregulating the expression of PDCD4, thus exerting a tumor suppressive function.<br> Increasing evidence has shown that FOXP3 is also expressed in tumor cells. However, the results of tumor FOXP3 is inconsistent and even the opposite. In some types of human cancers, the expression of FOXP3 is upregulated, and it can promote the development of cancers, leading to a poor prognosis. While in some other types of cancers, it is a different story. The reason for the contradictory data is unknown.<br> <br> Expression: FOXP3 is expressed in Tregs within the tumor microenvironment.<br> Prognosis: High FOXP3 expression can correlate with poor prognosis, as it may indicate immune evasion by the tumor.(but not always)<br>
711-	FoxP3+	↑	Forkhead box P3+			<b>FoxP3+</b> refers to cells that express the FoxP3 protein.<br> Immune Suppression: FOXP3+ Tregs are known for their ability to suppress immune responses. In the context of cancer, they can inhibit the activity of effector T cells and other immune cells, allowing tumors to evade immune detection.<br> Tumor Microenvironment: The presence of FOXP3+ Tregs in the tumor microenvironment is often associated with an immunosuppressive environment, which can facilitate tumor growth and metastasis.<br> <br> FOXP3+ Tregs in Specific Cancers<br> Breast Cancer:<br> Expression: FOXP3+ Tregs are present in the tumor microenvironment.<br> Prognosis: High levels of FOXP3+ Tregs are often linked to better prognosis, indicating a potential anti-tumor immune response.<br> Lung Cancer:<br> Expression: FOXP3+ Tregs are found in the tumor microenvironment.<br> Prognosis: Increased FOXP3+ Tregs can correlate with poor prognosis, suggesting immune evasion.<br> So expression is high, but prognosis can vary.<br>
1086-	frataxin	↓	frataxin			<b>Frataxin (has antioxidant properties)</b> is a mitochondrial protein primarily known for its role in:<br>     Iron–sulfur (Fe–S) cluster biogenesis.<br>     Iron homeostasis.<br>     Protection against oxidative stress.<br> Some studies have demonstrated that altered (often reduced) frataxin expression correlates with aggressive tumor features and poor patient outcomes. The rationale is that a decrease in frataxin might enhance oxidative damage and support a more aggressive phenotype.<br>
646-	FTH1	↑	ferritin heavy chain			<b>Ferritin</b> is a protein that stores iron in the body and is made up of two subunits, ferritin light chain (FTL) and ferritin heavy chain (FTH1).<br> Ferritin heavy chain 1 (FTH1) is one of the two subunits that make up the protein ferritin, which is responsible for storing iron in the body. FTH1 is encoded by the FTH1 gene, which is located on chromosome 11 in humans.<br> <br> FTH1 expression is often upregulated in various cancers and is generally associated with a poorer prognosis.<br>
645-	FTL	↑	ferritin light chain			<b>Ferritin</b> is a protein that stores iron in the body and is made up of two subunits, ferritin light chain (FTL) and ferritin heavy chain (FTH1).<br> <br> FTL expression is often elevated in various cancers and is generally linked to poorer prognosis.<br>
120-	FUBP1	↑	far upstream element (FUSE) binding protein 1	CGL-Driver Genes	TSG	<b>Far Upstream Element (FUSE) Binding Protein 1 (FUBP1)</b> is a transcription factor that plays a significant role in the regulation of gene expression, particularly in the context of cell growth and differentiation.<br> FUBP1 has been shown to promote cell proliferation and survival in various cancer types. Its overexpression can lead to enhanced tumor growth, while its downregulation may induce apoptosis in cancer cells.<br> generally considered an oncogene due to its role in promoting cell proliferation and survival, particularly through its regulation of the c-Myc oncogene.<br>
598-	Furin	↑	Furin			<b>Furin</b> is a type of protease enzyme that plays a crucial role in the processing and activation of various proteins involved in cell growth, differentiation, and survival.<br> Furin is overexpressed in many types of cancer, including breast, lung, colon, and prostate cancer. This overexpression can lead to the activation of various oncogenic proteins, such as growth factors, receptors, and adhesion molecules, which can promote tumor growth, invasion, and metastasis.<br> Furin can activate growth factors such as TGF-β, PDGF, and VEGF, which can promote tumor growth and angiogenesis.<br>
808-	G6PD	↑	Glucose-6-phosphate dehydrogenase			<b>Glucose-6-phosphate dehydrogenase (G6PD)</b> is an enzyme that plays a crucial role in the pentose phosphate pathway (PPP), a metabolic pathway that generates NADPH and pentoses from glucose-6-phosphate. G6PD is the first enzyme in the PPP and is responsible for catalyzing the conversion of glucose-6-phosphate to 6-phosphogluconate, producing NADPH in the process.<br> **** patients who receive intravenous ascorbate must be prescreened for glucose 6 phosphate dehydrogenase deficiency.<br> <br> G6PD expression is often elevated in various cancers and is generally linked to poorer prognosis.<br>
832-	G9a	↑	G9a		enzyme	<b>G9a</b> is a histone methyltransferase enzyme that plays a crucial role in various cellular processes, including gene expression, DNA repair, and cell cycle regulation. <br> G9a has been found to be overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. This overexpression is often associated with poor prognosis and reduced survival rates.<br>
1205-	GABA	↑	γ-aminobutyric acid			<b>– Some studies</b> have reported upregulated expression of certain GABA receptor subunits (e.g., GABA_A receptor subunits) in breast tumors.<br> <br> – Increased expression has been associated with enhanced cell proliferation and migration, with some reports linking this to a poorer prognosis.<br>
865-	GADD34	↑	Growth Arrest and DNA Damage-inducible protein 34			<b>GADD34 (Growth Arrest and DNA Damage-inducible protein 34)</b> is a protein that plays a crucial role in the regulation of cell growth, apoptosis, and DNA damage response.<br> GADD34 has been shown to promote tumor growth, invasion, and metastasis by facilitating cell proliferation, survival, and angiogenesis.<br> GADD34 has been found to be highly expressed in cancer stem cells, which are thought to be responsible for cancer initiation, progression, and recurrence.<br>
718-	GADD45A	↓	Growth Arrest and DNA Damage-inducible 45 alpha		TSG/protein	<b>GADD45A (Growth Arrest and DNA Damage-inducible 45 alpha)</b> is a protein that plays a crucial role in various cellular processes, including cell cycle regulation, DNA repair, and apoptosis.<br> GADD45A is a tumor suppressor gene that is often downregulated in various types of cancer, including breast, lung, and colon cancer.<br>
707-	Galectin-9	⇅			carbohydrate-binding proteins	<b>Galectin-9</b> is a member of the galectin family, a group of carbohydrate-binding proteins that play a role in various cellular processes, including cell signaling, adhesion, and immune responses.<br>
812-	GAPDH	↑	Glyceraldehyde-3-phosphate dehydrogenase		gene	<b>Glyceraldehyde-3-phosphate dehydrogenase (GAPDH)</b> is a housekeeping gene that encodes a protein involved in glycolysis, a metabolic pathway that converts glucose into energy. GAPDH is a crucial enzyme in the glycolytic pathway, and its expression is often used as a control gene in molecular biology experiments.<br> GAPDH has been shown to be overexpressed in various types of tumors, including breast, lung, colon, and prostate cancer. <br> Cancer cells often exhibit increased glycolysis, even in the presence of oxygen, a phenomenon known as the Warburg effect. GAPDH overexpression can contribute to this increased glycolysis.<br>
121-	GATA1	⇅	GATA binding protein 1 (globin transcription factor 1)	CGL-Driver Genes	TSG	<b>GATA1</b> is primarily known for its role in hematopoiesis and the development of erythroid cells, but it has also been implicated in various other cellular functions.<br> GATA1 can act as a tumor suppressor or an oncogene. In some cancers, its expression may be downregulated, leading to a loss of function that promotes tumor growth. In other cases, overexpression may contribute to oncogenic processes.<br>
122-	GATA2	↑	GATA binding protein 2	CGL-Driver Genes	Oncogene	<b>Members of the GATA family,</b> including GATA1, GATA2, GATA3, GATA4, GATA5, and GATA6.<br> GATA2 is a member of the GATA family of transcription factors and plays a critical role in various biological processes, including hematopoiesis (the formation of blood cells), immune system development, and organogenesis.<br> GATA2 can promote cell proliferation and survival in certain cancer types. It may activate downstream signaling pathways that lead to increased cell growth and resistance to apoptosis (programmed cell death).<br> high levels of GATA2 expression have been correlated with poor clinical outcomes, including reduced overall survival and increased risk of metastasis.<br>
123-	GATA3	?	GATA binding protein 3	CGL-Driver Genes	TSG	<b>GATA3</b> is often considered a key player in breast cancer biology. It is frequently expressed in luminal subtype breast cancers and is associated with a better prognosis.<br> GATA3 acts as a tumor suppressor. Its expression can inhibit the proliferation of cancer cells and promote differentiation, which is often lost in cancerous cells.<br> GATA3 is known to regulate the expression of estrogen receptors (ER), which are critical in the development and progression of ER-positive breast cancers. <br> <br> GATA3 is an important transcription factor with varying roles in different cancers. In breast cancer, it is generally associated with a favorable prognosis, while its role in other cancers can be more complex. <br>
966-	GCLC	⇅	Glutamate-Cysteine Ligase, Catalytic Subunit			<b>The GCLC gene (Glutamate-Cysteine Ligase, Catalytic Subunit)</b> is a key regulator of glutathione synthesis, and its expression has been studied in various types of cancer.<br> GCLC gene has been found to be:<br> Amplified in 15% of breast cancer cases<br> Mutated in 5% of lung cancer cases<br> Deleted in 10% of prostate cancer cases<br> Methylated in 20% of colorectal cancer cases<br>
965-	GCLM	↑	Glutamate-Cysteine Ligase Modifier Subunit			<b>The GCLM gene (Glutamate-Cysteine Ligase Modifier Subunit)</b> is a key regulator of glutathione synthesis, which is essential for maintaining cellular redox balance and protecting against oxidative stress. The GCLM gene is overexpressed in various types of cancer.<br> <br> GCLM gene is a key regulator of glutathione synthesis and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.<br>
136-	GDF15	↑	Growth differentiation factor 15	HalifaxProj(induce)		<b>Growth differentiation factor 15 (GDF15)</b> is a member of the transforming growth factor-beta (TGF-β) superfamily and is involved in various physiological processes, including inflammation, metabolism, and cell growth.<br> Elevated levels of GDF15 have been associated with various types of cancer, including breast, colorectal, prostate, and lung cancers. It is often considered a potential biomarker for cancer diagnosis, prognosis, and monitoring treatment response.<br> GDF15 can promote tumor growth and metastasis. It has been shown to enhance the survival of cancer cells under stress conditions, such as hypoxia and nutrient deprivation, which are common in the tumor microenvironment.<br> GDF15 is involved in metabolic regulation and can affect energy homeostasis. In cancer, it may contribute to cachexia (a syndrome characterized by weight loss and muscle wasting), which is often seen in advanced cancer patients.<br> Strategies to inhibit GDF15 or its signaling pathways may offer new avenues for cancer treatment <br> GDF15 is a stress-inducible member of the TGF‑β superfamily whose elevated expression in various cancers is often associated with higher tumor stage, metastasis, and poorer survival outcomes.<br>
989-	GDH	↑	Glutamate dehydrogenase			<b>Glutamate dehydrogenase (GDH)</b> is an enzyme that plays a central role in amino acid metabolism. It catalyzes the reversible oxidative deamination of glutamate to α-ketoglutarate and ammonia, linking amino acid metabolism with the tricarboxylic acid (TCA) cycle.<br> <br> Role of GDH in Metabolism<br> • GDH converts glutamate, a key amino acid, into α-ketoglutarate, which is an essential intermediate in the TCA cycle.<br> • By doing so, GDH contributes to energy production and anaplerosis (replenishment of TCA cycle intermediates).<br> •GDH activity can support cell survival when cancer cells rely not only on glycolysis (the Warburg effect) but also on glutaminolysis—using glutamine as a key nutrient for energy and biosynthesis.<br> <br> GDH Expression in Cancer<br> • Many cancers exhibit metabolic reprogramming to support rapid growth and proliferation. Some tumors have been found to upregulate GDH expression, allowing them to better use glutamine and glutamate as alternative energy sources.<br> • Elevated GDH expression can facilitate increased flux of glutamate into the TCA cycle, thereby supporting bioenergetic and biosynthetic demands of cancer cells.<br> • The increase in GDH activity may also help cancer cells adapt to nutrient-depleted or hypoxic microenvironments by offering metabolic flexibility.<br>
1161-	GFR	↓	glomerular filtration rate			<b>Glomerular filtration rate</b>—is primarily a clinical measure of kidney function rather than a molecular marker expressed by tumor cells. <br> <br> GFR as an Indicator of Overall Patient Health and Tolerance to Therapy<br> – GFR is routinely measured in patients with cancer, especially because many anticancer therapies (such as chemotherapy agents, targeted therapies, and immunotherapies) are renally excreted or can be nephrotoxic.<br> <br> – Lower GFR has been linked with poorer outcomes in various cancer types (for example, in patients with metastatic cancers, hematologic malignancies, or those undergoing major surgery) because it can limit the dosing and administration of effective therapies.<br> <br> – Poor kidney function (low GFR) may be an indicator of frailty or overall decreased organ reserve, which in turn can correlate with worse overall survival and increased mortality.<br>
348-	GIT1	?	GIT-1 gene		Gene	<b>G protein‐coupled receptor kinase</b>‐interacting protein 1 (GIT1) gene.<br> GIT1 as a modulator of Notch signalling and a guardian against breast cancer growth.<br>
434-	Gli	↑	GLI		protein/gene	<b>The GLI gene family</b> consists of three members: GLI1, GLI2, and GLI3. These genes encode transcription factors that play crucial roles in the Hedgehog signaling pathway, which is important for various developmental processes and cellular functions.<br> : In many cancers, aberrant activation of the Hedgehog signaling pathway leads to increased GLI expression. This can occur through mutations in Hedgehog pathway components or through the overexpression of Hedgehog ligands.<br> <br> -GLI factors are implicated in maintaining cancer stem cell populations. These cells often drive tumor recurrence, metastasis, and resistance to therapy because they have self-renewal capabilities. The overactivation of GLI may, therefore, help sustain these subpopulations within tumors.<br> <br> Elevated GLI expression levels can serve as a prognostic marker in certain cancers, indicating a more aggressive disease and poorer outcomes.<br>
124-	Gli1	↑	glioma-associated oncogene homolog 1		HH	<b>Gli family zinc-finger</b> transcription factors; GLI1‐dependent target genes (CyclinD1, Bcl‐2, Foxm1) <br> <br> Glioma-associated oncogene homolog 1 (GLI1) is a transcription factor that plays a significant role in the Hedgehog signaling pathway, which is crucial for cell growth, differentiation, and tissue patterning during embryonic development.<br> GLI1 can promote tumor growth and survival by regulating the expression of genes involved in cell proliferation, apoptosis, and angiogenesis. Its overexpression has been associated with aggressive tumor behavior and poor prognosis in several cancer types.<br> ts overexpression is often associated with aggressive tumor behavior, poor prognosis, and resistance to therapy<br>
353-	GLI2	?	GLI2			<b>GLI1, GLI2, and GLI3</b> are key downstream effectors of the Hh signaling pathway, acting as nuclear transcription factors that bind to promoters to regulate target gene expression. Highly expressed genes in human gliomas.<br>
354-	GLI3	?	GLI3			<b>GLI1, GLI2, and GLI3</b> are key downstream effectors of the Hh signaling pathway, acting as nuclear transcription factors that bind to promoters to regulate target gene expression. Highly expressed genes in human gliomas.<br>
125-	GLO-I	↑	glyoxalase I			<b>GLO-I, or glyoxalase I,</b> is an enzyme that plays a crucial role in the detoxification of reactive carbonyl species, particularly methylglyoxal, which is a byproduct of various metabolic processes.<br> Elevated levels of GLO-I in cancer cells can help them cope with these toxic byproducts, promoting cell survival and proliferation.<br> High levels of GLO-I may be associated with tumor progression and poor prognosis in certain types of cancer. <br> Inhibiting GLO-I could sensitize cancer cells to chemotherapy and other treatments by increasing their vulnerability to oxidative stress.<br> Many studies have reported that GLO-I is overexpressed in several types of cancers, including breast, lung, prostate, colorectal, and pancreatic cancers. This overexpression is often associated with aggressive tumor behavior and poor prognosis.<br>
639-	GLO1	↑	Glyoxalase 1 enzymne			<b>GLO1 (Glyoxalase 1)</b> is an enzyme that plays a crucial role in the detoxification of advanced glycosylation end-products (AGEs) and other reactive carbonyl species. Elevated GLO1 expression has been observed in various types of cancer, including breast, lung, and colon cancer. GLO1 is thought to contribute to cancer progression by promoting cell proliferation, survival, and metastasis.<br> GLO1 is overexpressed in various types of cancer, including breast, lung, colon, prostate, ovarian, and pancreatic cancer.<br>
127-	GLS	↑	glutaminase			<b>Glutaminase</b> is an enzyme that plays a crucial role in the metabolism of glutamine, an amino acid that is often utilized by cancer cells for growth and proliferation. In many cancers, including glioblastoma, leukemia, and certain types of solid tumors, glutamine metabolism is upregulated, allowing cancer cells to meet their increased energy and biosynthetic demands.<br> Glutamine Addiction: Many cancer cells exhibit a phenomenon known as "glutamine addiction," where they rely heavily on glutamine for survival and growth. This is particularly evident in rapidly proliferating tumors.<br> Glutaminase catalyzes the conversion of glutamine to glutamate, which can then enter various metabolic pathways, including the tricarboxylic acid (TCA) cycle. This process is essential for providing energy and building blocks for nucleotides and amino acids.<br> Inhibitors of glutaminase are being investigated in preclinical and clinical studies as a means to starve cancer cells of glutamine and inhibit their growth.<br> <br> GLS expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in supporting the metabolic needs of cancer cells.<br>
126-	glucoNG	↑	gluconeogenesis			<b>Gluconeogenesis</b> is the metabolic pathway through which organisms synthesize glucose from non-carbohydrate precursors. This process is crucial for maintaining blood glucose levels, especially during fasting or intense exercise. In the context of cancer, gluconeogenesis can play a significant role in tumor metabolism and growth.<br> Cancer cells often exhibit altered metabolic pathways, a phenomenon known as the Warburg effect, where they preferentially use glycolysis for energy production even in the presence of oxygen. However, gluconeogenesis can also be upregulated in certain cancer types, providing a source of glucose to support rapid cell proliferation.<br> Cancer cells can utilize various substrates for gluconeogenesis, including lactate, amino acids (especially alanine and glutamine), and glycerol. This allows tumors to generate glucose even when dietary glucose is limited.<br> Hormones such as glucagon and cortisol can stimulate gluconeogenesis. In cancer, the dysregulation of these hormones can contribute to altered glucose metabolism.<br> Key Enzymes in Gluconeogenesis<br> Pyruvate Carboxylase (PC)<br> Phosphoenolpyruvate Carboxykinase (PEPCK)<br> Fructose-1,6-bisphosphatase (FBPase)<br> Glucose-6-phosphatase (G6Pase)<br> <br> The expression of gluconeogenic enzymes is often altered in various cancers, and their upregulation is generally associated with poorer prognosis.<br>
1278-	glucose	↑	glucose			<b>Glucose</b><br>
623-	GlucoseCon	↑	Glucose Consumption			<b>Glucose consumption</b> is often elevated in cancer cells due to an increased reliance on glycolysis for energy production, even in the presence of oxygen. This phenomenon, known as the Warburg effect, is a metabolic shift that allows cancer cells to rapidly proliferate and survive in nutrient-poor environments.<br> <br> The increased glucose consumption in cancer cells can be detected using positron emission tomography (PET) scans, which measure the uptake of a glucose analog labeled with a radioactive tracer.<br>
1244-	glut	↑	glutamine			<b>Glutamine</b> is an amino acid that fuels various metabolic pathways, supporting bioenergetics, biosynthesis, and redox balance in cancer cells. <br> <br> -Many breast tumors exhibit glutamine addiction, relying on enhanced glutamine uptake and metabolism to support rapid proliferation.<br> <br> -In many tumor types—such as breast, lung, colorectal, liver, and pancreatic cancers—enhanced glutamine metabolism is often associated with a more aggressive phenotype, therapy resistance, and poorer patient outcomes.<br>
566-	GLUT1	↑	Glucose Transporter 1		protein	<b>Also known as SLC2A1</b> <br> An important hallmark in cancer cells is the increase in glucose uptake. GLUT1 is an important target in cancer treatment because cancer cells upregulate GLUT1, a membrane protein that facilitates the basal uptake of glucose in most cell types, to ensure the flux of sugar into metabolic pathways.<br> GLUT1 is a member of the facilitated glucose transporter family and is widely expressed in various tissues, including red blood cells, brain, and cancer cells.<br> GLUT1 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glucose uptake and energy production in cancer cells.<br> GLUT1 is a protein that facilitates the transport of glucose across cell membranes. GLUT1 plays a role in the regulation of glucose metabolism in diabetes.<br> GLUT1 plays a role in the regulation of glucose metabolism in diabetes.<br> GLUT1 is also known to be involved in the Warburg effect.<br> GLUTs are expressed 10–12-fold higher in cancer cells than in healthy tissues, especially in highly proliferative and malignant tumors.<br> <br> Downregulators:<br> -Resveratrol: associated with reduced GLUT1 expression.<br> -Curcumin: downregulate GLUT1 in various cancer cell lines<br> -Quercetin: downregulating the expression and function of GLUT1.<br> -EGCG: suppress GLUT1 expression<br> -Berberine: linked to decreased expression or activity of GLUT1.<br>
1198-	GLUT2	↝	Glucose Transporter 2			<b>GLUT2</b> is a member of the facilitative glucose transporter family, primarily responsible for the uptake of glucose and other hexoses into cells.<br> <br> – In cancers like HCC, lower GLUT2 expression sometimes correlates with poorer differentiation and a more aggressive phenotype. As cancer cells shift toward a more glycolytic metabolism, they may rely less on the regulated glucose uptake observed in normal cells, and decreased GLUT2 expression can serve as a marker of this metabolic reprogramming.<br>
928-	GLUT3	↑	GLUT3			<b>GLUT3</b> is a member of the glucose transporter family, which plays a crucial role in glucose uptake and metabolism in cells. In the context of cancer, GLUT3 has been found to be overexpressed in various types of tumors, including brain, breast, colon, and lung cancers.<br> GLUT3 is overexpressed in cancer cells compared to normal cells. This overexpression is thought to contribute to the increased glucose uptake and metabolism observed in cancer cells.<br>
774-	GLUT4	↑	Glucose Transporter 4			<b>GLUT4 (Glucose Transporter 4)</b> is a protein that plays a crucial role in glucose metabolism by facilitating the transport of glucose across cell membranes. GLUT4 is a member of the facilitated glucose transporter family and is primarily expressed in adipose tissue and skeletal muscle.<br> GLUT4 has been shown to be overexpressed in many types of tumors, and its expression has been linked to cancer cell growth, survival, and metastasis.<br> GLUT4 is involved in the regulation of glucose metabolism in cancer cells, and its overexpression has been shown to promote glucose uptake and energy production in cancer cells. <br> GLUT4 promotes glucose uptake and energy production in cancer cells.<br> GLUT4 expression is linked to poor prognosis in various types of cancer.<br>
1083-	GlutaM	↑	Glutaminolysis			<b>Glutaminolysis</b> is the metabolic process through which glutamine, a non-essential amino acid, is catabolized to support cellular energy and biosynthesis. In many cancer cells, glutaminolysis is upregulated to meet the high demands for energy (ATP), biosynthetic precursors, and maintenance of redox balance. <br> Key Steps and Abbreviations in Glutaminolysis.<br> Glutamine (Gln): uptake of glutamine from the extracellular environment.<br> Glutaminase (GLS):Converts glutamine into glutamate by deamination. GLS overexpressed in cancers.<br> Glutamate (Glu): further converted into α-ketoglutarate (α-KG).<br> Glutamate Dehydrogenase (GDH): Catalyzes the conversion of glutamate to α-KG, feeding the tricarboxylic acid cycle (TCA, also known as Krebs cycle).<br> α-Ketoglutarate (α-KG):α-KG is a key intermediate in the TCA cycle. <br> Additional Players:<br> c-Myc: A transcription factor frequently overexpressed in cancer that upregulates genes involved in glutamine uptake and metabolism, including GLS.<br> SLC1A5 (ASCT2): A glutamine transporter that is often upregulated in cancer to facilitate increased glutamine uptake.<br> <br> In many cancers there is an upregulation of key glutaminolysis components:GLS, SLC1A5, c-Myc. Many studies have found that overexpression of glutaminolysis-related enzymes (especially GLS) correlates with aggressive tumor behavior and poor patient outcomes.<br>
128-	GlutMet	↑	Glutamine metabolism			<b>Glutamine metabolism</b> plays a significant role in cancer biology, as many cancer cells exhibit altered metabolic pathways to support their rapid growth and proliferation. <br> Glutamine is a non-essential amino acid that serves as a vital nutrient for many cells, including cancer cells. It is involved in various metabolic processes, including protein synthesis, nucleotide synthesis, and energy production.<br> Warburg Effect: Cancer cells often rely on aerobic glycolysis (the Warburg effect) for energy production, even in the presence of oxygen. Glutamine metabolism can complement this process by providing intermediates for the tricarboxylic acid (TCA) cycle, which is crucial for energy production and biosynthesis.<br> Inhibitors of glutaminase (an enzyme that converts glutamine to glutamate) and other metabolic pathways are being explored in preclinical and clinical settings.<br> <br> Key Enzymes in Glutamine Metabolism<br> Glutaminase (GLS)<br> Glutamate Dehydrogenase (GLUD)<br> Glutamine Synthetase (GS)<br> Asparagine Synthetase (ASNS)<br> Aminotransferases (e.g., GPT, GOT)<br> <br> The expression of enzymes involved in glutamine metabolism is often elevated in various cancers and is generally associated with poorer prognosis. <br>
1192-	glyC	↑	glycogen			<b>Glycogen</b><br> • Many tumors, especially under hypoxic or nutrient-deprived conditions, reprogram their metabolism to store glycogen as an energy reserve.<br> <br> • Increased glycogen accumulation can serve as a survival mechanism that helps cancer cells endure metabolic stress, which, in turn, may be associated with more aggressive behavior.<br> <br> • Prognosis:<br> – In certain cancers (e.g., certain glioblastomas, pancreatic cancers), high intratumoral glycogen content has been associated with adaptation to hypoxia and resistance to therapy.<br> – Such adaptations often correlate with a poorer prognosis, as the glycogen reservoir helps support tumor progression under adverse conditions.<br>
129-	Glycolysis	↑	Glycolysis			<b>Glycolysis</b> is a metabolic pathway that converts glucose into pyruvate, producing a small amount of ATP (energy) in the process. It is a fundamental process for cellular energy production and occurs in the cytoplasm of cells. In normal cells, glycolysis is tightly regulated and is followed by aerobic respiration in the presence of oxygen, which allows for the efficient production of ATP.<br> In cancer cells, however, glycolysis is often upregulated, even in the presence of oxygen. This phenomenon is known as the Warburg Mutations in oncogenes (like MYC) and tumor suppressor genes (like TP53) can alter metabolic pathways, promoting glycolysis and other anabolic processes that support cell growth.effect.<br> Acidosis: The increased production of lactate from glycolysis can lead to an acidic microenvironment, which may promote tumor invasion and suppress immune responses.<br> <br> Glycolysis is a hallmark of malignancy transformation in solid tumor, and LDH is the key enzyme involved in glycolysis.<br> <br> Pathways:<br> -GLUTs, HK2, PFK, PK, PKM2, LDH, LDHA, PI3K/AKT/mTOR, AMPK, HIF-1a, c-MYC, p53, SIRT6, HSP90α, GAPDH, HBT, PPP, Lactate Metabolism, ALDO<br> <br> Natural products targeting glycolytic signaling pathways https://pmc.ncbi.nlm.nih.gov/articles/PMC9631946/<br> Alkaloids:<br> -Berberine, Worenine, Sinomenine, NK007, Tetrandrine, N-methylhermeanthidine chloride, Dauricine, Oxymatrine, Matrine, Cryptolepine<br> <br> Flavonoids: -Oroxyline A, Apigenin, Kaempferol, Quercetin, Wogonin, Baicalein, Chrysin, Genistein, Cardamonin, Phloretin, Morusin, Bavachinin, 4-O-methylalpinumisofavone, Glabridin, Icaritin, LicA, Naringin, IVT, Proanthocyanidin B2, Scutellarin, Hesperidin, Silibinin, Catechin, EGCG, EGC, Xanthohumol.<br> <br> Non-flavonoid phenolic compounds:<br> Curcumin, Resveratrol, Gossypol, Tannic acid.<br> <br> Terpenoids:<br> -Cantharidin, Dihydroartemisinin, Oleanolic acid, Jolkinolide B, Cynaropicrin, Ursolic Acid, Triptolie, Oridonin, Micheliolide, Betulinic Acid, Beta-escin, Limonin, Bruceine D, Prosapogenin A (PSA), Oleuropein, Dioscin.<br> <br> Quinones:<br> -Thymoquinone, Lapachoi, Tan IIA, Emodine, Rhein, Shikonin, Hypericin<br> <br> Others:<br> -Perillyl alcohol, HCA, Melatonin, Sulforaphane, Vitamin D3, Mycoepoxydiene, Methyl jasmonate, CK, Phsyciosporin, Gliotoxin, Graviola, Ginsenoside, Beta-Carotene.<br>
535-	GM-CSF	↑	Granulocyte-macrophage colony-stimulating factor			<b>Also called G-CSF</b><br> A cytokine that drives the generation of myeloid cell subsets including neutrophils, monocytes, macrophages, and dendritic cells in response to stress, infections, and cancers.<br> While too little GM-CSF prevents the appropriate production of innate immune cells and subsequent activation of adaptive anti-cancer immune responses, too much of GM-CSF can exhaust immune cells and promote cancer growth. The consequences of GM-CSF signaling in cancer progression are a function of the levels of GM-CSF, the cancer type, and the tumor microenvironment. In this review, we first discuss the secretion of GM-CSF, signaling downstream of the GM-CSF receptor, and GM-CSF’s role in modulating myeloid cell homeostasis.<br> <br> GM-CSF expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in promoting an immunosuppressive tumor microenvironment and supporting tumor growth. Its ability to influence the behavior of immune cells, particularly macrophages, can contribute to tumor progression and metastasis.<br>
130-	GNA11/Gαq	↑	guanine nucleotide binding protein (G protein), alpha 11 (Gq class)	CGL-Driver Genes	Oncogene	<b>Guanine nucleotide-binding proteins,</b> commonly known as G proteins, play a crucial role in cellular signaling pathways. The Gq class of G proteins, which includes the alpha subunit Gαq, is involved in various physiological processes, including the regulation of phospholipase C (PLC) activity, leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers are important for calcium signaling and activating protein kGαq signaling can promote cell proliferation and survival through various pathways, including the activation of the MAPK/ERK pathway. Dysregulation of these pathways can lead to uncontrolled cell growth, a hallmark of cancer.<br> inase C (PKC), which can influence cell growth, differentiation, and survival.<br> <br> GNA11 expression and its associated signaling pathways are often altered in various cancers, and these changes can be linked to poorer prognosis due to their role in promoting tumor growth and survival.<br>
131-	GNAQ	↑	guanine nucleotide binding protein (G protein), q polypeptide	CGL-Driver Genes	Oncogene	<b>GNAQ</b> gene are commonly associated with certain cancers, particularly uveal melanoma. These mutations often lead to constitutive activation of the G protein, promoting uncontrolled cell growth and survival.<br> <br> GNAQ expression and mutations are often associated with various cancers, particularly melanoma and uveal melanoma, where they serve as important prognostic markers. The presence of GNAQ mutations is linked to aggressive tumor behavior and poorer outcomes. <br>
132-	GNAS	↑	GNAS complex locus	CGL-Driver Genes	Oncogene	<b>The GNAS complex locus</b> is a genomic region located on chromosome 20 that encodes the GNAS gene, which is responsible for producing the Gs alpha subunit of the G protein involved in various signaling pathways, particularly those related to hormone signaling and cell growth. <br> Activating mutations in the GNAS gene can lead to constitutive activation of signaling pathways, which may promote cell proliferation and survival. These mutations are often found in certain types of tumors, including pituitary adenomas and some thyroid cancers.<br> <br> GNAS expression and mutations are associated with various cancers, particularly pituitary adenomas and some thyroid and colorectal cancers. The presence of GNAS mutations can influence tumor behavior and may be linked to poorer outcomes in certain contexts. <br>
873-	GNLY	⇅	Granulysin		Granulysin	<b>Granulysin</b> is a Granulysin that is expressed by cytotoxic T cells and natural killer cells, and plays a crucial role in the immune system's ability to eliminate infected cells and tumor cells.<br>
402-	GnT-V	↑	N-acetylglucosaminyltransferase-V			<b>Activity of glycosyltransferase GnT-V</b> correlates with cancer malignancy and poor prognosis. GnT-V, or N-acetylglucosaminyltransferase V (also known as MGAT5), is an enzyme involved in the glycosylation of proteins, specifically in the addition of N-acetylglucosamine (GlcNAc) residues to the core structure of N-glycans. This enzyme plays a significant role in the modification of glycoproteins, which can influence various cellular processes, including cell adhesion, signaling, and immune response. <br> <br> GnT-V expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in promoting tumor aggressiveness and metastasis. Its involvement in glycosylation processes can influence cell behavior, including adhesion and migration, which are critical for cancer progression.<br>
502-	GP1BB	↑	glycoprotein Ib beta subunit gene			<b>The GP1BB gene,</b> also known as the glycoprotein Ib beta subunit gene, is a gene that encodes a protein subunit of the glycoprotein Ib-IX-V complex. This complex is a receptor for von Willebrand factor (VWF) and plays a crucial role in the process of platelet adhesion and activation.<br> GP1BB is overexpressed in certain types of cancer, including breast, lung, and colon cancer. This overexpression was associated with increased tumor cell proliferation, migration, and invasion, suggesting that GP1BB may contribute to the aggressive behavior of cancer cells.<br>
1286-	GPI	↑	Glucose-6-Phosphate Isomerase			<b>GPI (Glucose-6-Phosphate Isomerase)</b><br> – GPI catalyzes the reversible interconversion of glucose-6-phosphate and fructose-6-phosphate, a critical step in glycolysis and gluconeogenesis.<br> <br> GPI can contribute to the enhanced glycolytic activity observed in many tumors.<br> <br> – Tumor Aggressiveness: Elevated levels of GPI (both intracellular and secreted forms) have been correlated with enhanced invasiveness and metastatic potential, particularly in cancers such as breast, lung, and gastric cancers.<br> <br> – Poor Outcomes: Increased GPI may serve as a marker for aggressive tumor phenotypes and is often associated with poorer clinical outcomes. In some studies, high serum levels of GPI/AMF have been proposed as indicative of advanced disease and a worse prognosis.<br>
418-	GPx	↑	Glutathione peroxidases			<b>Glutathione peroxidases (GPXs)</b> are crucial antioxidant enzymes, counteracting reactive oxygen species (ROS). <br> Glutathione peroxidase (GPx) refers to a family of antioxidant enzymes that play a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. There are several isoforms of GPx, including GPx1, GPx2, GPx3, and GPx4, each with distinct tissue distributions and functions. <br> GPX overexpression promotes proliferation and invasion in cancer cells. Glutathione peroxidase-1 (GPX1), the most abundant isoform, contributes to invasion, migration, cisplatin resistance, and proliferation in various cancers.<br> <br> GPx expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance. <br>
133-	GPX1	↑	Glutathione Peroxidase			<b>Widely and abundantly expressed antioxidant enzyme</b><br> Glutathione peroxidase (GPx) is an important antioxidant enzyme that plays a crucial role in protecting cells from oxidative stress by catalyzing the reduction of hydrogen peroxide and organic peroxides. It utilizes glutathione, a tripeptide composed of glutamine, cysteine, and glycine, as a substrate to carry GPx is part of the body's antioxidant defense system. By reducing oxidative stress, GPx may help prevent the initiation and progression of cancer. Some studies suggest that higher levels of GPx activity are associated with a lower risk of certain cancers.<br> The tumor microenvironment is often characterized by increased oxidative stress. GPx can influence the behavior of cancer cells and their interactions with surrounding cells. In some cases, cancer cells may upregulate GPx to survive in this oxidative environment, which can contribute to tumor growth and resistance Inhibiting GPx in certain cancer types may sensitize tumor cells to chemotherapy and radiation therapy by increasing oxidative stress.to therapy.<br> <br> GPX1 is widely expressed in various tissues and is particularly important in maintaining cellular redox balance. GPX1 expression is often elevated in various cancers and is generally associated with poorer prognosis due to its role in protecting cancer cells from oxidative stress and contributing to treatment resistance. <br>
134-	GPX3	↓	Glutathione Peroxidase 3			<b>GPX3, or Glutathione Peroxidase 3,</b> is an enzyme that plays a crucial role in protecting cells from oxidative stress by reducing hydrogen peroxide and other peroxides.<br> Glutathione peroxidase 3 (GPX3) is another member of the glutathione peroxidase family, primarily found in extracellular spaces and secreted into the bloodstream. It plays a crucial role in protecting cells from oxidative stress by reducing hydrogen peroxide and organic peroxides. <br> GPX3 can act as a tumor suppressor, as its expression is often downregulated in various types of cancer, including breast, prostate, and colorectal cancers. Lower levels of GPX3 may lead to increased oxidative stress, which can promote cancer cell proliferation and survival.<br> Conversely, in some contexts, GPX3 may also be associated with cancer progression, particularly in the tumor microenvironment, where it can influence the behavior of cancer cells and their interactions with surrounding tissues.<br> <br> GPX3 expression is often decreased in various cancers and is generally associated with poorer prognosis due to its role in protecting cells from oxidative stress. The downregulation of GPX3 can lead to increased oxidative damage, promoting tumor progression and aggressiveness. <br>
643-	GPX4	↑	Glutathione Peroxidase 4			<b>GPX4 (Glutathione Peroxidase 4)</b> is a selenoprotein that plays a crucial role in the regulation of ferroptosis, a form of programmed cell death characterized by the iron-dependent accumulation of lipid reactive oxygen species (ROS). <br> GPX4 has been found to be upregulated in several tumor types, promoting cancer cell survival and resistance to therapy. For instance, GPX4 overexpression has been observed in renal cell carcinoma, pancreatic ductal adenocarcinoma, and triple-negative breast cancer, among others. -GPX4 is known as a lipid peroxidation inhibitor protein, and its antioxidant effect is closely related to ferrous iron<br>
135-	GPX8	↑	Glutathione Peroxidase 8			<b>GPX8, or Glutathione Peroxidase 8,</b> is a member of the glutathione peroxidase family of enzymes, which play a crucial role in protecting cells from oxidative stress by reducing hydrogen peroxide and other peroxides.<br> Glutathione peroxidase 8 (GPX8) is a member of the glutathione peroxidase family, which plays a role in protecting cells from oxidative stress by reducing hydrogen peroxide and organic peroxides. GPX8 is unique among the GPX family as it is primarily localized in the endoplasmic reticulum (ER) and is involved in maintaining redox homeostasis within this organelle. <br> <br> GPX8 is involved in the cellular response to oxidative stress, and its expression can be altered in various cancers. While some studies suggest that increased GPX8 levels may correlate with tumor aggressiveness and resistance to oxidative stress, the specific prognostic implications of GPX8 in cancer are still being investigated.<br>
390-	GR	⇅	glucocorticoid receptors			<b>Glucocorticoid receptors (GR),</b> also known as NR3C1 (nuclear receptor subfamily 3, group C, member 1), are a type of steroid hormone receptor that mediates the effects of glucocorticoids, which are steroid hormones involved in various physiological processes, including metabolism, immune response, and stress response. <br> In certain cancer subtypes such as gynaecological cancers (endometrial and ovarian) and early stage, untreated triple negative breast cancers, high GR expression is linked with cancer progression and therefore a poorer patient prognosis.<br> <br> Glucocorticoid receptors play a significant role in various cancers, and their expression can have complex prognostic implications. In some cancer types, high GR expression is associated with better outcomes, while in others, it may correlate with aggressive disease and treatment resistance. The relationship between glucocorticoid receptor expression and cancer prognosis can vary depending on the specific cancer type, stage, and other molecular factors.<br>
871-	GranA	⇅	granzyme A		serine protease	<b>Granzyme A</b> is a serine protease that is expressed by cytotoxic T cells and natural killer cells, and plays a crucial role in the immune system's ability to eliminate infected cells and tumor cells. Granzyme A works in conjunction with perforin to induce apoptosis (programmed cell death) in target cells.<br> <br> In the context of cancer, granzyme A has been found to have both positive and negative effects.<br>
872-	GranB	⇅	Granzyme B		serine protease	<b>Granzyme B</b> is a serine protease that is expressed by cytotoxic T cells and natural killer cells, and plays a crucial role in the immune system's ability to eliminate infected cells and tumor cells. Granzyme B works in conjunction with perforin to induce apoptosis (programmed cell death) in target cells.<br> <br> In the context of cancer, granzyme B has been found to have both positive and negative effects.<br> <br> Granzyme B is an important marker of immune activity in the tumor microenvironment, and its expression is often associated with better prognosis in various cancers. High levels of Granzyme B in tumor-infiltrating lymphocytes indicate an effective anti-tumor immune response, which can help control tumor growth and improve patient outcomes. <br>
1007-	GREM1	↑	Gremlin1			<b>GREM1</b> encodes Gremlin1, a secreted glycoprotein that acts primarily as an antagonist of bone morphogenetic proteins (BMPs). By modulating BMP signaling, Gremlin1 plays an important role in embryonic development, tissue differentiation, and organogenesis. In cancer, dysregulation of GREM1 can impact cell proliferation, differentiation, and migration, contributing to tumor progression.<br> <br> Its aberrant overexpression in various cancers correlates with more aggressive tumor features and poorer patient outcomes, positioning it as a promising prognostic biomarker.<br>
600-	GRP58	↑	GRP58/ERp57			<b>Also known as ERp57</b><br> A molecular chaperone that plays a crucial role in the endoplasmic reticulum (ER) stress response.<br> ERp57 is often overexpressed, which can contribute to tumor growth and survival.<br> ERp57 can promote cancer cell proliferation, migration, and invasion by regulating various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways. Additionally, ERp57 can also inhibit apoptosis (programmed cell death) in cancer cells, which can contribute to tumor progression.<br>
356-	GRP78/BiP	↑	P-glycoprotein			<b>GRP78</b> (Pgp, BiP or ERp72) is a central regulator of endoplasmic reticulum (ER) function due to its roles in protein folding and assembly, targeting misfolded protein for degradation, ER Ca(2+)-binding and controlling the activation of trans-membrane ER stress sensors.<br> -GRP78 protein, a marker for endoplasmic reticulum stress<br> The association of P-gp and inhibition of cell death in cancerous cells has also been reported in several studies including in hepatocellular, colorectal, prostate cancer, and gastric cancer. Although counterintuitive due to its prominent role in cancer resistance, P-gp has been linked to favorable prognosis.<br> ERp72 can promote cancer cell proliferation, migration, and invasion by regulating various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways. Additionally, ERp72 can also inhibit apoptosis (programmed cell death) in cancer cells, which can contribute to tumor progression. Overexpressed in: Breast, lung colorectal, prostrate, ovarian, pancreatic.<br>
905-	GRP94	↑	Glucose-Regulated Protein 94			<b>GRP94 (Glucose-Regulated Protein 94)</b> is a molecular chaperone that plays a crucial role in protein folding, assembly, and quality control in the endoplasmic reticulum (ER). It is also known as GP96 or HSP90B1.<br> High GRP94 expression(common) is associated with poor prognosis, increased tumor aggressiveness, and reduced overall survival.<br>
1065-	GS3Kβ	⇅	Glycogen Synthase Kinase 3 Beta			<b>GSK3β</b> is a serine/threonine kinase involved in numerous cellular processes including glycogen metabolism, cell cycle regulation, and apoptosis.<br> It is a key regulator in several pathways such as Wnt/β-catenin, PI3K/AKT, and NF-κB, which are central to oncogenic processes and tumor progression.<br> <br> Glycogen Synthase Kinase 3 Beta (GSK3β) is a critical kinase involved in diverse cellular processes that govern tumor cell survival, proliferation, and apoptosis. Its expression and activity are frequently altered in cancer, with both overactivation and inhibition linked to adverse outcomes, depending on the cellular context and specific signaling environment.<br>
1305-	GSDMC	↑	Gasdermin C			<b>GSDMC (Gasdermin C)</b> is a member of the gasdermin family, proteins that have garnered attention for their role in pyroptosis—a form of programmed cell death associated with inflammation—and for their emerging implications in cancer.<br> <br> • Several studies have reported dysregulation of GSDMC in a range of tumors. In some cancers, such as colorectal, lung, and gastric cancers, GSDMC expression has been found to be upregulated compared to normal tissue.<br> <br> • The increased expression of GSDMC in these cancers is thought to be linked not only to cell death pathways but also to the modulation of the tumor microenvironment, potentially influencing tumor progression.<br> <br> • Elevated GSDMC expression in some cancers has been associated with more aggressive tumor behavior. For instance, higher levels of GSDMC have been correlated with advanced stages, increased metastasis, and poorer overall survival in certain studies.<br>
1317-	GSDMD	↓	gasdermin D			<b>GSDMD</b> is best known for its central role in mediating pyroptosis, a form of inflammatory programmed cell death.<br> <br> -Some studies suggest that increased GSDMD expression and associated pyroptosis may improve local antitumor immunity.<br> -Some preclinical studies indicate that enhanced pyroptosis via GSDMD activation may correlate with a better prognosis, likely through improved immune-mediated clearance of tumor cells.<br>
1311-	GSDME	↓	gasdermin E			<b>Gasdermin E (GSDME),</b> also known as DFNA5<br> <br> - GSDME is best known for its role in mediating pyroptosis, a form of inflammatory programmed cell death.<br> <br> - In several cancers, GSDME is frequently silenced by promoter hypermethylation.<br>
1216-	GSDME-N	↓	N‐terminal domain of Gasdermin E			<b>GSDME‐N fragment (the N‐terminal domain of Gasdermin E)</b><br> • GSDME (Gasdermin E) is a member of the gasdermin family and is cleaved by caspase‐3 during apoptosis. This cleavage releases the N‐terminal fragment (GSDME‐N), which can form pores in the cell membrane, inducing pyroptosis—a proinflammatory form of programmed cell death.<br> <br> • Some studies have found that high levels of GSDME expression, which can lead to increased GSDME‐N formation upon cleavage, correlate with enhanced pyroptosis in tumor cells.<br> • In select breast cancer cohorts, increased pyroptosis may contribute to a more robust local immune response, potentially correlating with improved prognosis.<br> <br> - Formation of the GSDME‐N fragment and its associated induction of pyroptosis might, in some contexts, favor a more robust anti‐tumor immune response and potentially better clinical outcomes.<br>
137-	GSH	↑	Glutathione			<b>Glutathione (GSH)</b> is a thiol antioxidant that scavenges reactive oxygen species (ROS), resulting in the formation of oxidized glutathione (GSSG). Decreased amounts of GSH and a decreased GSH/GSSG ratio in tissues are biomarkers of oxidative stress.<br> Glutathione is a powerful antioxidant found in every cell of the body, composed of three amino acids: cysteine, glutamine, and glycine. It plays a crucial role in protecting cells from oxidative stress, detoxifying harmful substances, and supporting the immune system.<br> cancer cells can have elevated levels of glutathione, which may help them survive in the oxidative environment created by the immune response and chemotherapy. This can make cancer cells more resistant to treatment.<br> While glutathione can be obtained from certain foods (like fruits, vegetables, and meats), its absorption from supplements is debated. Some people take N-acetylcysteine (NAC) or other precursors to boost glutathione levels, but the effects on cancer prevention or treatment are still being studied.<br> Depleting glutathione (GSH) to raise reactive oxygen species (ROS) is a strategy that has been explored in cancer research and therapy. <br> Many cancer cells have altered redox states and may rely on GSH to survive. Increasing ROS levels can induce stress in these cells, potentially leading to cell death.<br> Certain drugs and compounds can deplete GSH levels. For example, agents like buthionine sulfoximine (BSO) inhibit the synthesis of GSH, leading to its depletion.<br> Cancer cells tend to exhibit higher levels of intracellular GSH, possibly as an adaptive response to a higher metabolism and thus higher steady-state levels of reactive oxygen species (ROS).<br> <br> "...intracellular glutathione (GSH) exhibits an astounding antioxidant activity in scavenging reactive oxygen species (ROS)..."<br> "Cancer cells have a high level of GSH compared to normal cells."<br> "...cancer cells are affluent with high antioxidant levels, especially with GSH, whose appearance at an elevated concentration of ∼10 mM (10 times less in normal cells) detoxifies the cancer cells." "Therefore, GSH depletion can be assumed to be the key strategy to amplify the oxidative stress in cancer cells, enhancing the destruction of cancer cells by fruitful cancer therapy."<br> <br> The loss of GSH is broadly known to be directly related to the apoptosis progression.<br>
104-	GSH/GSSG	↑	GSH/GSSG ratio			<b>Glutathione (GSH)</b> is a ubiquitous tripeptide antioxidant that plays a key role in mitigating oxidative damage. GSH is oxidized by ROS to form a homodimer disulfide (GSSG).<br> The ratio between GSH and GSSG can be used as a metric to define the redox state of a cell, and imbalances in this ratio leading to excess GSSG can cause cell death.<br> GSH/GSSG ratio can be altered in various types of cancer, including breast, lung, colon, and prostate cancer. In general, increased GSH levels and decreased GSSG levels are associated with cancer progression and poor prognosis.<br>
385-	GSK‐3β	⇅	Glycogen synthase kinase (GSK)3β			<b>GSK3β</b> is a crucial member of the Wnt/β-catenin-, hedgehog (Hh)-, notch- and c-myc-mediated major pro-oncogenic pathways, while also being a negative regulator of epithelial–mesenchymal transition (EMT). Accumulating evidence defines GSK3β as a potential therapeutic target in cancer, thus encouraging the development of GSK3β inhibitors for cancer treatment.<br> Glycogen synthase kinase 3 beta (GSK-3β) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis. Its expression and activity have been implicated in several types of cancer, often with varying prognostic implications. <br> <br> In many cancers, decreased GSK-3β activity is associated with poor prognosis, while in others, increased activity may correlate with aggressive disease. <br>
633-	GSR	↑	Glutathione Reductase			<b>Glutathione reductase</b> is an enzyme that plays a crucial role in maintaining the balance of glutathione, a powerful antioxidant found in cells. Glutathione is involved in various cellular processes, including detoxification, cell signaling, and protection against oxidative stress. Glutathione reductase helps maintain the levels of reduced glutathione (GSH) in cells. Cancer cells often have elevated levels of glutathione reductase, which allows them to maintain high levels of GSH and resist oxidative stress.<br> Glutathione reductase has been shown to promote cell proliferation and survival in cancer cells. Elevated levels of glutathione reductase have been found in various types of cancer, including breast, lung, and colon cancer.<br> Several studies have shown that inhibiting glutathione reductase can increase the sensitivity of cancer cells to chemotherapy and radiation therapy, and may also induce apoptosis in cancer cells.<br>
1271-	GSS	↑	Glutathione Synthetase			<b>GSS (Glutathione Synthetase)</b> is a key enzyme in the synthesis of glutathione (GSH), an essential intracellular antioxidant that protects cells from oxidative stress and contributes to detoxification processes. <br> -GSS catalyzes the second step in glutathione synthesis, converting γ-glutamylcysteine and glycine into glutathione.<br> <br> -Elevated expression of GSS has been observed in certain tumors as cancer cells adapt to high ROS levels. This adaptation can help protect malignant cells from apoptosis and contribute to chemoresistance.<br>
1212-	GSSG	↓	oxidized glutathione			<b>GSSG (oxidized glutathione)</b> is a component of the cellular redox system rather than a protein or signaling molecule produced de novo. Its levels, often evaluated along with its reduced counterpart (GSH), serve as an important index of cellular oxidative stress and redox balance.<br> <br> – GSSG is generated when glutathione (GSH) neutralizes reactive oxygen species (ROS) by donating electrons; in doing so, GSH is oxidized to GSSG.<br> <br> – The GSH/GSSG ratio is a sensitive marker of the intracellular redox state. Under conditions of oxidative stress (commonly observed in many cancers), this ratio often shifts toward increased GSSG.<br> <br> – Elevated GSSG levels (or an increased GSSG/GSH ratio) can indicate that cancer cells are under oxidative stress, which has implications both for cancer progression and for sensitivity to certain treatments.<br>
1091-	GSTA1	↑	Glutathione S-Transferase A1			<b>GSTA1</b> belongs to the glutathione S-transferase (GST) superfamily of enzymes. These enzymes catalyze the conjugation of glutathione (GSH) to a variety of electrophilic substrates, thereby aiding in their detoxification.<br> By facilitating the detoxification of reactive metabolites, carcinogens, and drugs, GSTA1 helps protect cells against oxidative stress and chemical-induced damage.<br> In tumor cells, upregulation of GSTA1 may be a defensive response to increased oxidative stress. While this can protect normal cells, in a tumor setting, enhanced detoxification may allow cancer cells to survive in a hostile microenvironment.<br> Elevated levels of GSTA1 have been linked to resistance to chemotherapy. As GSTA1 helps metabolize and clear chemotherapeutic agents, its overexpression in tumors can contribute to treatment resistance<br> -GSTA1 expression levels are being evaluated as a prognostic marker. In some studies, its overexpression has correlated with aggressive tumor behavior, higher rates of recurrence, and reduced overall survival.<br>
601-	GSTP1/GSTπ	↑	Glutathione S-transferase pi 1			<b>An enzyme</b> that plays a crucial role in the detoxification of various substances, including carcinogens. It is also involved in the regulation of cellular processes, such as cell growth, differentiation, and apoptosis.<br> GSTP1 is overexpressed in various types of cancer, including prostate, breast, lung, and colon cancer. The overexpression of GSTP1 has been associated with cancer progression, metastasis, and poor prognosis.<br>
1153-	GSTs	↑	Glutathione S-transferases			<b>Glutathione S-transferases (GSTs)</b> are a family of phase II detoxification enzymes that play key roles in catalyzing the conjugation of glutathione (GSH) to a wide range of electrophilic compounds. This family includes multiple isoenzymes (e.g., GST-α, GST-μ, GST-π) with tissue-specific expression patterns and overlapping as well as distinct substrate specificities.<br> <br> -GSTs are important for detoxifying potentially harmful compounds, including products of oxidative stress, environmental toxins, and chemotherapeutic agents.<br> -They contribute to the cellular defense mechanism against oxidative damage and help maintain cellular redox balance.<br> -Beyond detoxification, GSTs can modulate cell signaling pathways, potentially affecting cell proliferation, apoptosis, and drug resistance.<br> <br> -GST-π is commonly upregulated in several cancers such as breast, lung, colorectal, and hematologic malignancies.<br> -Elevated expression of specific GST isoenzymes—most notably GST-π—has been associated with a poorer prognosis in several cancer types. This is often linked to resistance to chemo- or radiotherapy, as higher GST activity can lead to more efficient detoxification of these agents, reducing their cytotoxic effects.<br> -In contrast, reduced GST expression in some contexts might indicate a less robust detoxification system, which can correlate with increased sensitivity to oxidative stress and possibly a less aggressive tumor phenotype.<br>
1203-	GSTZ1	⇅	Glutathione S-transferase zeta 1			<b>GSTZ1 (Glutathione S-transferase zeta 1)</b> is an enzyme involved in phase II detoxification and tyrosine catabolism.<br> <br> Several studies have reported differences in GSTZ1 expression across cancer types. In some malignancies, GSTZ1 expression is downregulated, which might diminish the cell's ability to detoxify carcinogens and reactive oxygen species (ROS). In other instances, GSTZ1 expression may be upregulated, possibly reflecting an adaptive response to increased oxidative stress or drug exposure.<br> <br> -Enzyme responsible for conversion of DCA to its inactive metabolite, glyoxylate, is downregulated in liver cancer and upregulated in some breast cancers, leading to abnormal expression of the protein. <br> (desireable to inhibit GSTZ1 to reduce resistance to DCA)<br>
1297-	GTPBP4	↑	GTP-binding protein 4			<b>GTPBP4 (GTP-binding protein 4)</b><br> GTPBP4 is a member of the GTPase family and is involved in ribosome biogenesis and RNA processing.<br> <br> -Elevated levels of GTPBP4 are linked to enhanced cell proliferation, which may contribute to tumor aggressiveness.<br> -Some studies correlate high GTPBP4 expression with poorer clinicopathological outcomes, suggesting its potential as a prognostic marker in breast cancer.<br>
350-	GutMicro	↝	Gut Microbiota			<b>Gut microbiome</b> may affect responses to numerous forms of cancer therapy.<br> The gut microbiota plays a multifaceted role in cancer biology, influencing tumor development, progression, and patient prognosis. Dysbiosis and specific microbial populations have been linked to various cancers, with implications for patient outcomes. While the relationship between gut microbiota and cancer prognosis is an active area of research, it holds promise for the development of microbiome-based biomarkers and therapeutic strategies in oncology. <br>
642-	H19	↑	H19 long non-coding RNA (lncRNA)			<b>H19</b> is a long non-coding RNA (lncRNA) that is often overexpressed in various types of cancer, including gastric, colorectal, and bladder cancer.<br>
138-	H2O2	↑	Hydrogen peroxide (H2O2)			<b>H2O2</b> is a reactive oxygen species (ROS) that can induce oxidative stress in cells. While low levels of ROS can promote cell signaling and proliferation, high levels can lead to DNA damage, apoptosis (programmed cell death), and other cellular dysfunctions. This dual role means that H2O2 can contribute to cancer development and progression, as oxidative stress can lead to mutations and genomic instability.<br> H2O2 can enhance the effectiveness of certain chemotherapeutic agents by increasing oxidative stress in cancer cells. Additionally, localized delivery of H2O2 has been explored as a means to selectively target and kill cancer cells while sparing normal cells.<br> Cancer cells often exhibit altered metabolism, leading to increased production of reactive oxygen species, including H2O2. This can result from enhanced mitochondrial activity, increased glycolysis, or other metabolic adaptations that are characteristic of cancer.<br> <br> <br> Reported H2O2 concentrations for representative compounds.<br> <table> <thead> <tr><th>   Prooxidant   </th><th>       Dose       </th><th>            Cell Line            </th><th>H2O2 Produced</th></tr> </thead> <tbody> <tr><td>EGCG</td><td>50 µM</td><td>Jurkat</td><td>~1 µM</td></tr> <tr><td>EGCG</td><td>10 µM</td><td>HCT116 and HT29</td><td>1.5 µM</td></tr> <tr><td>EGCG</td><td>100 µM</td><td>Jurkat</td><td>20 µM</td></tr> <tr><td>Quercetin</td><td>70 µM</td><td>HT29</td><td>2 µM</td></tr> <tr><td>Menadione</td><td>10 µM</td><td>Jurkat</td><td>20 µM</td></tr> <tr><td>Plumbagin</td><td>4 µM</td><td>SiHA and HeLa</td><td>1 mM</td></tr> <tr><td>β-Lap</td><td>1 µM</td><td>HL-60</td><td>70 µM</td></tr> <tr><td>Doxorubicin</td><td>1 µM</td><td>PC3</td><td>38 pM</td></tr> <tr><td>Ascorbic Acid </td><td>1 mM</td><td>HL-60</td><td>161 µM</td></tr> <tr><td>Ascorbic Acid</td><td>0.2–2.0 mM</td><td>Lymphoma</td><td>20–120 µM</td></tr> <tr><td>Ascorbic Acid</td><td>i.v. 0.5 mg/g</td><td>Rats</td><td>0–20 µM</td></tr> <tr><td>Ascorbic Acid</td><td>i.p. 4.0 g/kg</td><td>Mice tumor</td><td>> 125 µM</td></tr> <tr><td>TiO2</td><td>10 µg/mL</td><td>HepG2</td><td>150 nmol/mL</td></tr> <tr><td>Paclitaxel</td><td>100 nM</td><td>MCF7</td><td>600 nM</td></tr> <tr><td>Paclitaxel</td><td>100 nM</td><td>HL-60</td><td>1100 nM</td></tr> </tbody> </table> <br> Note: many products at lower concentrations act as antioxidants, instead of Prooxidants.<br> <br> Generally, increased hydrogen peroxide and oxidative stress are associated with poor outcomes, while the specific context and cellular environment can modulate its effects.<br>
1281-	H2S	⇅	hydrogen sulfide			<b>In the liver,</b> H₂S is produced endogenously through the enzymatic activity of cystathionine β‐synthase (CBS), cystathionine γ‐lyase (CSE), and the mitochondrial 3-mercaptopyruvate sulfurtransferase (3-MST).<br> <br> – In the liver, H₂S participates in maintaining metabolic homeostasis and controlling oxidative stress, with a dual role depending on its concentration and context.<br> <br> At low-to-moderate levels, H₂S generally supports cytoprotection, angiogenesis, and pro-survival pathways. In contrast, high levels of H₂S can trigger oxidative stress and cytotoxicit.<br>
890-	H3	↑	Histone 3			<b>Histone 3 (H3)</b> is a protein that is a component of chromatin, the complex of DNA and proteins that makes up the chromosomes in the nucleus of eukaryotic cells. H3 is one of the five main histone proteins, and it plays a crucial role in the regulation of gene expression and the maintenance of chromatin structure.<br> H3 has been found to be overexpressed in various types of cancer, including breast, prostate, lung, and colon cancer.<br>
139-	H3F3A	↑	H3F3A	CGL-Driver Genes	Oncogene	<b>H3 histone, family 3B (H3.3B);</b> H3 histone, family 3A pseudogene; H3 histone, family 3A; similar to H3 histone, family 3B; similar to histone H3.3B<br> H3F3A is a gene that encodes a variant of the histone H3 protein, which is a crucial component of chromatin in eukaryotic cells. Histones play a significant role in the regulation of gene expression and the structural organization of DNA.<br> Alterations or mutations in the H3F3A gene, particularly in the context of specific amino acid substitutions, have been associated with certain types of cancer, most notably gliomas, which are tumors that occur in the brain and spinal cord. <br> <br> H3F3A plays a significant role in cancer biology, particularly through its involvement in chromatin regulation and gene expression. Mutations in H3F3A, especially the H3.3K27M variant, are associated with aggressive tumor behavior and poor prognosis in several cancer types, particularly glioblastoma and pediatric brain tumors. <br> While H3F3A itself is not an oncogene, the mutations in this gene can drive oncogenic pathways and contribute to the development and progression of tumors.<br>
889-	H3K18	↑	Histone 3 Lysine 18			<b>H3K18 (Histone 3 Lysine 18)</b> is a histone modification that has been implicated in various types of cancer. Histone modifications play a crucial role in regulating gene expression, and H3K18 is one of the most well-studied histone modifications.<br> H3K18 has been found to be overexpressed in various types of cancer, including breast, prostate, lung, and colon cancer.<br> Targeting H3K18 with small molecule inhibitors has been shown to be a promising therapeutic strategy for cancer treatment.<br>
973-	H3K27ac	↑	histone H3 lysine 27 acetylation			<b>H3K27ac</b> is a histone modification that is associated with active gene expression. Here are some key points about H3K27ac and its relationship to cancer:<br> <br> Elevated in: breast, lung, colon, prostate ,Cancer stem cells and progenitor cells.<br> High levels of H3K27ac are associated with poor prognosis in:Breast,Lung,CRC cancer.<br> Low levels of H3K27ac are associated with good prognosis in:<br> Certain types of leukemia and lymphoma (correlated with increased overall survival and disease-free survival).<br> <br> H3K27ac has been shown to play a role in the regulation of various oncogenes, including:<br> MYC<br> Cyclin D1<br> CDK4<br> <br> Inhibition of H3K27ac has been shown to suppress tumor growth and induce apoptosis in various types of cancer.<br>
891-	H4	↑	Histone 4			<b>Histone 4 (H4)</b> is a protein that is a component of chromatin, the complex of DNA and proteins that makes up the chromosomes in the nucleus of eukaryotic cells. H4 is a core histone that plays a crucial role in the regulation of chromatin structure and gene expression.<br> H4 has been found to be overexpressed in various types of cancer, including breast, prostate, lung, and colon cancer.<br>
1109-	Half-Life	∅	Half-Life			<b>For many drugs, the half-life</b> is the time it takes for half of the drug’s active substance to be eliminated from the bloodstream.<br> In medicine, knowing a drug’s half-life helps in designing treatment regimens that reduce adverse effects.<br>
886-	HATs	↑	histone acetyltransferases			<b>Histone acetyltransferases (HATs)</b> are a family of enzymes that play a crucial role in the regulation of gene expression by modifying chromatin structure. HATs transfer acetyl groups to the lysine residues of histone proteins, which are the main components of chromatin. This modification, known as histone acetylation, leads to the relaxation of chromatin structure, allowing for increased access of transcription factors to DNA and promoting gene expression.<br> HATs is overexpressed in cancers with poor prognosis.<br>
1168-	HbA1c	↑	hemoglobin A1c			<b>HbA1c</b> is a glycated form of hemoglobin that reflects the average blood glucose concentration over the previous two to three months.<br> – It is commonly used in the clinical management of diabetes to monitor long-term blood sugar control.<br> – Since hyperglycemia has been linked to oxidative stress and low-grade inflammation, HbA1c serves as an indirect indicator of metabolic dysfunction.<br> <br> – Cancer cells often reprogram metabolic pathways to support growth; systemic metabolic status (reflected by HbA1c) can influence tumor behavior.<br> – Chronic hyperglycemia (and thus elevated HbA1c) may lead to a pro-inflammatory state and increased production of reactive oxygen species (ROS), potentially affecting tumor progression.<br> <br> – Several clinical studies have found that cancer patients with high HbA1c levels tend to have poorer overall survival compared to those with controlled glycemic levels.<br> – Elevated HbA1c may be associated with more aggressive tumor characteristics, treatment resistance, and higher incidence of treatment-related complications.<br> – In cancers such as colorectal, breast, and pancreatic, metabolic disturbances indicated by increased HbA1c have been linked to unfavorable prognostic outcomes.<br>
742-	HCAR1	↑	Hydroxycarboxylic acid receptor 1			<b>Also known as GPR81 (G protein-coupled receptor 81)</b><br> HCAR-1 is a G protein-coupled receptor that plays a role in various physiological processes, including metabolism, inflammation, and immune response.<br> HCAR-1 is overexpressed in certain types of cancer, such as breast, colon, and prostate cancer.<br>
140-	HDAC	↑	Histone deacetylases			<b>Enzymes</b> involved in regulating gene expression by removing acetyl groups from histones, the proteins around which DNA is wrapped.<br> -Many cancers exhibit altered expression levels of HDACs, which can contribute to the dysregulation of genes involved in cell growth, survival, and differentiation.<br> -HDACs can repress the expression of tumor suppressor genes, leading to uncontrolled cell proliferation and survival. This repression can be a key factor in the development and progression of cancer.<br> -HDAC inhibitors (HDACi) have been developed and are being investigated for their ability to reactivate silenced genes, induce cell cycle arrest, and promote apoptosis in cancer cells.<br> -HDAC1, HDAC2): Often overexpressed in various cancers, including breast, prostate, and colorectal cancers. Their overexpression is associated with poor prognosis.<br> -HDAC4, HDAC5): These may have both oncogenic and tumor-suppressive roles depending on the context and cancer type.<br> -While HDACs are not classified as traditional oncogenes, their overexpression and activity can contribute to oncogenic processes.<br> -HDAC inhibitor works by preventing the removal of acetyl groups from histones, thereby modulating gene expression, influencing cell behavior, and potentially reversing aberrant gene silencing seen in various diseases.<br> -HDAC inhibitors can help reactivate these genes, thereby inhibiting growth and inducing apoptosis in cancer cells.<br>
982-	HDAC1	↑	Histone Deacetylase 1			<b>HDAC1</b> is an enzyme that removes acetyl groups from histone tails, resulting in chromatin condensation and transcriptional repression.<br> – By modulating the acetylation status of histones, HDAC1 plays a key role in regulating gene expression involved in cell cycle progression, differentiation, apoptosis, and DNA repair.<br> – Aberrant expression or activity of HDAC1 has been linked to several cancers.<br> – Overexpression of HDAC1 can lead to the repression of tumor suppressor genes, thereby promoting oncogenic programs and contributing to tumor progression.<br> – HDAC1 is often associated with a more aggressive tumor phenotype and, in some contexts, a poorer clinical prognosis.<br> Therapeutic Targeting:<br> – HDAC inhibitors (HDACis) have emerged as anticancer agents; they work by inhibiting HDAC activity to restore acetylation levels on histones and nonhistone proteins.<br>
1127-	HDAC10	↑	HDAC10			<b>HDAC10</b> (a member of the histone deacetylase family) <br> • HDAC10 is involved in chromatin remodeling, gene expression, DNA repair, and autophagy.<br> • Its activity may influence tumor cell survival, invasiveness, and resistance to therapy through regulation of these pathways.<br> <br> HDAC10 appears to play a context-dependent role in various cancers. In several studies—particularly in ovarian and lung cancers—elevated HDAC10 expression has been associated with poorer clinical outcomes, including chemoresistance and increased tumor aggressiveness.<br>
904-	HDAC11	⇅	Histone Deacetylase 11			<b>HDAC11 (Histone Deacetylase 11)</b> is a member of the histone deacetylase family, which plays a crucial role in regulating gene expression by modifying chromatin structure. HDAC11 has been implicated in various types of cancer, and its expression has been associated with cancer prognosis.<br> Prognostic significance:<br> • High HDAC11 expression: Associated with poor prognosis and increased risk of metastasis in breast, gastric, lung, and pancreatic cancers.<br> • Low HDAC11 expression: Linked to poor prognosis and increased risk of recurrence in colorectal, hepatocellular carcinoma, ovarian, and prostate cancers.<br>
984-	HDAC2	↑	Histone Deacetylase 2			<b>HDAC2</b> is a member of the class I histone deacetylase family that removes acetyl groups from lysine residues on histone proteins.<br> <br> • This deacetylation usually promotes chromatin compaction, leading to transcriptional repression of genes involved in cell differentiation, apoptosis, and cell cycle regulation.<br> • HDAC2, along with its relatives HDAC1 and others, is often found as part of multiprotein corepressor complexes that regulate gene expression in both normal and cancer cells.<br> <br> 2. Role of HDAC2 in Cancer<br> • Overexpression and Dysregulation:<br> – In several types of cancer, HDAC2 is overexpressed or dysregulated, contributing to an altered transcriptional profile.<br> – Elevated HDAC2 levels can lead to the suppression of tumor suppressor genes and genes involved in cell-cycle checkpoints or apoptosis, facilitating tumor progression.<br> <br> • Impact on the Tumor Microenvironment:<br> – HDAC2 activity influences not only tumor cells but also the surrounding stromal and immune cells, affecting inflammatory responses and immune evasion strategies.<br>
1023-	HDAC3	↑	Histone Deacetylase 3			<b>HDAC3</b> is an enzyme belonging to the class I histone deacetylases and plays a key role in transcriptional regulation by removing acetyl groups from histone tails.<br> This deacetylase activity leads to chromatin condensation and generally results in transcriptional repression.<br> HDAC3 is involved in multiple cellular processes, including cell cycle regulation, apoptosis, and differentiation.<br> <br> HDAC3 is frequently found to be overexpressed in several cancer types, including breast, colorectal, liver, lung, and hematological malignancies.<br> Elevated HDAC3 levels have been associated with the repression of tumor suppressor genes and deregulation of proliferative pathways.<br>
407-	HDAC4	↑	Histone deacetylases			<b>HDAC4</b> overexpression is associated with higher tumor grade, advanced clinical stage and poor survival. HDAC4 promotes proliferation and G1/S cell cycle progression in EC cells by inhibiting cyclin-dependent kinase (CDK) inhibitors p21 and p27 and up-regulating CDK2/4 and CDK-dependent Rb phosphorylation.<br> <br> HDAC4 is often overrepresented and associated with poor prognosis.<br> HDAC Inhibitors: Given the role of HDAC4 in cancer, HDAC inhibitors (HDACi) are being explored as potential therapeutic agents.<br>
1097-	HDAC8	↑	Histone deacetylase 8			<b>Histone deacetylase 8 (HDAC8)</b> is one of the class I histone deacetylases involved in the removal of acetyl groups from histone and non-histone proteins. This deacetylation alters chromatin structure and gene expression and has been associated with various cellular processes including proliferation, apoptosis, and differentiation. Aberrant expression or activity of HDAC8 has been reported in several types of cancer where it can influence tumor behavior and prognosis.<br> <br> – Studies report increased HDAC8 levels in certain aggressive tumor subtypes. <br> – Overexpression is often correlated with higher tumor grade, increased cell proliferation, and poorer patient outcomes.<br> <br> HDAC8 overexpression is frequently associated with a more aggressive disease course and poorer prognosis in several types of cancer, including breast cancer, neuroblastoma, AML, and colorectal cancer. Its role in deacetylation and chromatin remodeling makes it an attractive target for therapeutic intervention, and ongoing studies aim to clarify its full prognostic and predictive value in cancer management.<br>
63-	HDL	↓	HDL cholesterol			<b>High-density lipoprotein (HDL) cholesterol</b> is often referred to as "good" cholesterol because it helps transport cholesterol away from the arteries and back to the liver, where it can be processed and removed from the body. <br> Some research suggests that higher levels of HDL cholesterol may be associated with a lower risk of certain types of cancer. This could be due to HDL's role in reducing inflammation and oxidative stress, both of which are linked to cancer development.<br> Other studies have indicated that very high levels of HDL cholesterol might be associated with an increased risk of certain cancers. <br> While higher levels of HDL cholesterol are generally associated with cardiovascular health and may have protective effects against certain cancers, the evidence is mixed, and the implications for cancer risk and prognosis vary by cancer type.<br>
412-	HEC1	↑	highly expressed in cancer 1			<b>HEC1 (also known as HEC1 or NDC80)</b> is a protein that is part of the NDC80 complex, which is crucial for the proper functioning of the mitotic spindle during cell division. It plays a significant role in the attachment of microtubules to kinetochores, ensuring accurate chromosome segregation during mitosis. Dysregulation of HEC1 has been implicated in various cancers, and its expression levels can have prognostic implications.<br> Hec1 is often overexpressed in cancers with poor prognosis.<br> Hec1 is significantly upregulated in cervical cancer tissues and associated with poor prognosis in cervical cancer patients.<br> <br> Its overexpression is associated with various cancers, including breast, lung, ovarian, and colorectal cancers, often correlating with poor prognosis and aggressive tumor behavior. While HEC1 itself is not classified as a traditional oncogene, its dysregulation contributes to oncogenic processes, making it a potential target for therapeutic intervention and a candidate biomarker for cancer prognosis.<br>
487-	HemoG	↓	Hemoglobin			<b>Hemoglobin (often abbreviated as "HemoG")</b> is a protein in red blood cells responsible for transporting oxygen throughout the body. While hemoglobin itself is not directly linked to cancer, there are several important aspects of its relationship with cancer that are worth noting:<br> Many cancer patients experience anemia, which is a condition characterized by low levels of hemoglobin. This can be due to various factors, including the cancer itself, chemotherapy, or nutritional deficiencies.<br> Tumors often have regions of low oxygen (hypoxia) due to inadequate blood supply. Hypoxia can promote tumor progression, metastasis, and resistance to therapy. Hemoglobin's role in oxygen transport makes it a critical factor in the tumor microenvironment, as oxygen levels can influence cancer cell behavior.<br> Changes in hemoglobin levels or the presence of specific hemoglobin variants may serve as potential biomarkers for certain cancers.<br>
403-	heparanase	↑	heparan sulfate degrading endoglycosidase			<b>Heparanase</b> is an enzyme that cleaves heparan sulfate, a component of the extracellular matrix and cell surface proteoglycans. It plays a significant role in various biological processes, including cell migration, angiogenesis, and tissue remodeling. <br> Heparanase promotes tumor cell proliferation, growth and angiogenesis within the tumor cells, at the cell surface, and within the tumor microenvironment. <br> Heparanase expression is enhanced in almost all cancers.<br> Heparanase degrades heparan sulfate chains, leading to the release of growth factors and cytokines that can promote tumor growth, angiogenesis, and metastasis.<br> By remodeling the extracellular matrix, heparanase facilitates tumor cell invasion and migration, contributing to the metastatic spread of cancer.<br> <br> Heparanase is often overexpressed in various tumors, and its activity is associated with increased tumor aggressiveness and poor clinical outcomes.<br>
1179-	hepatoP	↓	hepatoprotective			<b>Hepatoprotective</b> is the ability of a chemical substance to prevent damage to the liver.<br> <br> Grapefruit:<br> -hepatoprotective potential has emerged from the study of naringenin and naringin.<br> Blueberries/cranberries:<br> -proanthocyanidins<br> Grape:<br> Nopal (Cactus pear) and tuna (Cactus pear fruit) “Opuntia ficus-indica”:<br> Chamomile (Matricaria chamomilla or Chamomilla recutita):<br> Silymarin (Silybum marianum):<br> Blue green algae spirulina :<br> Propolis (bee glue):<br> <br> POLYSACCHARIDES<br> β-glucans<br>
359-	HER2/EBBR2	↑	Human epidermal growth factor receptor 2			<b>Also called erbB-2 (or ERb-2)</b> -Receptor tyrosine-protein kinase <br> HER2 is a protein that helps breast cancer cells grow quickly.<br> HER2/neu protein is a receptor tyrosine kinase that is normally involved in cell growth and division. However, in some cancers, the HER2/neu gene is overexpressed or mutated, leading to an overproduction of the protein. This can cause cells to grow and divide uncontrollably, leading to tumor formation.<br>
438-	HEY1	↑	Hairy/enhancer-of-split related with YRPW motif 1			<b>HEY1</b> (Hairy/enhancer-of-split related with YRPW motif 1) is a gene that plays a role in various biological processes, including development and cell differentiation. <br> HEY1 has been found to be overexpressed in various cancers, which can contribute to tumor growth and progression. It may influence pathways related to cell proliferation, apoptosis (programmed cell death), and angiogenesis (the formation of new blood vessels). <br> HEY1 is often found to be overexpressed in several cancers, including breast cancer, colorectal cancer, and glioblastoma. This overexpression can be associated with aggressive tumor behavior and poor prognosis.<br> <br> Its overexpression is associated with various cancers, including breast, lung, colorectal, and hepatocellular carcinoma, often correlating with poor prognosis and aggressive tumor behavior.<br>
186-	HGF/c-Met	↑	met proto-oncogene (hepatocyte growth factor receptor)	CGL-Driver Genes	Oncogene	<b>Hepatocyte growth factor (HGF)</b> and its high-affinity receptor, mesenchymal epithelial transition factor (c-Met), are closely related to the onset, progression, and metastasis of multiple tumors. The HGF/c-Met axis is involved in cell proliferation, movement, differentiation, invasion, angiogenesis, and apoptosis by activating multiple downstream signaling pathways.<br> HGF (Hepatocyte Growth Factor) and its receptor c-Met play significant roles in various biological processes, including cell growth, motility, and differentiation. Their involvement in cancer has been extensively studied, as the HGF/c-Met signaling pathway is often dysregulated in many types of tumors<br> : The HGF/c-Met pathway can promote tumor cell proliferation and survival. When HGF binds to c-Met, it activates several downstream signaling pathways, including the PI3K/Akt and MAPK pathways, which are crucial for cell survival and growth.<br> c-Met is associated with increased invasive and metastatic potential of cancer cells. The activation of this pathway can enhance the motility of cancer cells, allowing them to invade surrounding tissues and spread to distant sites.<br> Tumors that overexpress c-Met may evade the effects of treatment, leading to poor patient outcomes.<br>
141-	HH	↑	Hedgehog signaling	CGL-CF	HH	<b>Sonic hedgehog,</b> Shh; Indian hedgehog, Ihh; Desert hedgehog, Dhh ; Hh signaling pathway is able to regulate the EMT. Hh signaling-related factors, SHH, SMO and GLI1.<br> Hedgehog signaling is a crucial pathway in embryonic development and tissue homeostasis, but its dysregulation has been implicated in various cancers. The Hedgehog (Hh) pathway is activated by the binding of Hedgehog ligands (such as Sonic Hedgehog, Indian Hedgehog, and Desert Hedgehog) to their receptors, primarily Patched (PTCH) and Smoothened (SMO). <br> <br> -Hedgehog pathway is crucial for the maintenance of stem cell populations. When deregulated, it can help sustain cancer stem cells (CSCs) that possess self-renewal properties, drive tumor recurrence, and confer resistance to conventional therapies.<br> <br> -Inhibitors of the pathway, such as vismodegib and sonidegib, have been developed and are used in clinical settings, particularly for treating advanced BCC and other Hedgehog-dependent tumors.<br>
142-	HIF-1	↑	HIF-1 signaling	HalifaxProj(inhibit)		<b>Hypoxia-inducible factor 1 (HIF-1)</b> is a transcription factor that plays a crucial role in cellular responses to low oxygen levels (hypoxia). It is composed of two subunits: HIF-1α and HIF-1β. Under normal oxygen conditions, HIF-1α is rapidly degraded, but in hypoxic conditions, it stabilizes, translocates to the nucleus, and dimerizes with HIF-1β to activate the transcription of various genes involved in processes such as angiogenesis, metabolism, and cell survival.<br> HIF-1α is often overexpressed due to the hypoxic microenvironment created by rapid tumor growth and inadequate blood supply. This upregulation allows cancer cells to adapt to low oxygen levels. HIF-1 regulates the expression of numerous target genes involved in angiogenesis (e.g., VEGF), glucose metabolism (e.g., GLUT1), cell survival, and invasion. The activation of these genes promotes tumor growth and metastasis.<br> However, HIF-1 is expressed in pathological conditions such as cancer and obesity.<br>
143-	Hif1a	↑	HIF1α/HIF1a			<b>Hypoxia-Inducible-Factor 1A</b> (HIF1A gene, HIF1α, HIF-1α protein product)<br> -Dominantly expressed under hypoxia(low oxygen levels) in solid tumor cells<br> -HIF1A induces the expression of vascular endothelial growth factor (VEGF)<br> -High HIF-1α expression is associated with Poor prognosis<br> -Low HIF-1α expression is associated with Better prognosis<br> <br> -Functionally, HIF-1α is reported to regulate glycolysis, whilst HIF-2α regulates genes associated with lipoprotein metabolism.<br> -Cancer cells produce HIF in response to hypoxia in order to generate more VEGF that promote angiogenesis<br> <br> <a href="https://www.sciencedirect.com/science/article/pii/S2090123223000668" >Key mediators of aerobic glycolysis regulated by HIF-1α. </a><br> -GLUT-1 → regulation of the flux of glucose into cells.<br> -HK2 → catalysis of the first step of glucose metabolism.<br> -PKM2 → regulation of rate-limiting step of glycolysis.<br> -Phosphorylation of PDH complex by PDK → blockage of OXPHOS and promotion of aerobic glycolysis.<br> -LDH (LDHA): Rapid ATP production, conversion of pyruvate to lactate;<br> <br> HIF-1α Inhibitors:<br> -Curcumin: disruption of signaling pathways that stabilize HIF-1α (ie downregulate).<br> -Resveratrol: downregulate HIF-1α protein accumulation under hypoxic conditions.<br> -EGCG: modulation of upstream signaling pathways, leading to decreased HIF-1α activity.<br> -Emodin: reduce HIF-1α expression. (under hypoxia).<br> -Apigenin: inhibit HIF-1α accumulation.<br>
1274-	HIF2a	↑	Hypoxia-Inducible Factor 2 alpha			<b>HIF-2α (Hypoxia-Inducible Factor 2 alpha),</b> also known as EPAS1, is a transcription factor that plays a key role in the cellular response to hypoxia (low oxygen conditions). In cancer, HIF-2α is involved in regulating genes that promote angiogenesis, metabolism, cell proliferation, and survival.<br> <br> -Tumors often experience hypoxia due to rapid cell growth outpacing vascular supply. This leads to the stabilization and upregulation of HIF-2α.<br> -Elevated HIF-2α expression has been observed in several cancer types, including renal cell carcinoma, glioma, lung, breast, and colorectal cancers.<br>
144-	Hippo	↓	Hippo signaling pathway	TCGA		<b>Hippo</b> signaling pathway is a crucial regulatory mechanism that controls cell growth, proliferation, and apoptosis (programmed cell death). It plays a significant role in organ size control and tissue homeostasis. <br> When the Hippo pathway is active, YAP and TAZ are phosphorylated by LATS1/2, leading to their retention in the cytoplasm and subsequent degradation. When the pathway is inactive, YAP and TAZ translocate to the nucleus, where they promote the expression of genes that drive cell proliferation and inhibit apoptosis.<br> In many cancers, the Hippo pathway is found to be inactivated, leading to the overactivation of YAP/TAZ. This results in uncontrolled cell growth and survival, contributing to tumorigenesis.<br>
145-	HIST1H3B	⇅	histone cluster 1, H3j, H3, H3h, H3g, H3f1, H3e, H3d, H3c, H3b, H3a, H2ad; histone cluster 2, H3a, H3c, H3d	CGL-Driver Genes	Oncogene	<b>A gene</b> that encodes a variant of histone H3, which is a protein that plays a crucial role in the structure and function of chromatin in eukaryotic cells. Histones are involved in the packaging of DNA into a compact, organized structure, allowing for proper gene regulation and expression. mutations in histone genes, including HIST1H3B, can be found in certain cancers, such as pediatric gliomas and other tumors. These mutations can lead to changes in the epigenetic landscape of the cells, contributing to tumorigenesis by affecting how genes are turned on or off.<br> Expression levels of histone genes, including HIST1H3B, can be upregulated or downregulated. This dysregulation can contribute to the cancerous phenotype by affecting the overall epigenetic landscape of the tumor cells.<br>
1232-	Histones	?	Histones			<b>Histones</b> play a crucial role in regulating gene expression, and this regulatory mechanism is central to many aspects of brain development, function, and plasticity.<br> <br> -Histone Acetylation: Often associated with active gene transcription. Enzymes known as histone acetyltransferases (HATs) add acetyl groups that reduce the positive charge on histones, weakening their interaction with the negatively charged DNA and thereby promoting gene expression.<br> -Histone Methylation: Depending on the specific amino acid residue and the number of methyl groups added, histone methylation can either activate or repress transcription. For instance, methylation on lysine 4 of histone H3 (H3K4me) is commonly linked to gene activation, whereas methylation on lysine 9 (H3K9me) is typically associated with gene repression.<br>
448-	HK1	↑	Hexokinase 1			<b>Accelerated glucose metabolism</b> is a common feature of cancer cells. Hexokinases catalyze the first committed step of glucose metabolism. HK1 (Hexokinase 1) is a key enzyme in glycolysis, catalyzing the phosphorylation of glucose to glucose-6-phosphate. It is critical for maintaining cellular energy homeostasis and is part of the metabolic reprogramming often observed in cancer cells.<br> <br> • In some tumors, HK1 is upregulated to meet the high glycolytic demands of rapidly proliferating cancer cells. However, the expression pattern can be context-dependent, with some cancers potentially showing moderate or variable HK1 levels compared to the normal tissue counterpart.<br> <br> • Enhanced HK1 expression supports the high glycolytic flux commonly seen in cancers (the Warburg effect), facilitating anabolic processes and thereby aiding in rapid cell proliferation and biomass accumulation.<br> <br> • Changes in HK1 expression can also alter the balance between glycolysis and oxidative phosphorylation, potentially impacting reactive oxygen species (ROS) production and cellular redox status in tumors.<br>
773-	HK2	↑	Hexokinase 2		enzyme	<b>HK2 (Hexokinase 2)</b> is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. HK2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.<br> HK2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.<br> HK2 is a key regulatory enzyme in the glycolytic pathway.<br> HK2 plays a role in the regulation of glucose metabolism in diabetes.<br> HK2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.<br> <br> HK2 Inhibitors:<br> -2DG<br> -Curcumin<br> -Resveratrol<br> -EGCG<br> -Berberine<br> -Methyl Jasmonate (MJ)<br> -Honokiol<br>
1116-	HLA	↓	Human Leukocyte Antigen (HLA) molecules			<b>Human Leukocyte Antigen (HLA)</b> molecules play a critical role in immune recognition, antigen presentation, and the regulation of immune responses. <br> <br> • HLA class I molecules (e.g., HLA-A, -B, -C) are expressed on nearly all nucleated cells and present endogenous antigens to CD8⁺ cytotoxic T lymphocytes.<br> • Downregulation or loss of HLA class I expression is a common immune evasion strategy employed by tumors.<br> <br> • Reduced HLA class I levels have been associated with poorer prognosis in several cancers, such as melanoma, colorectal, and lung cancers, because low expression hampers recognition and killing of tumor cells by cytotoxic T cells.<br> <br> • HLA class II molecules (e.g., HLA-DR, -DP, -DQ) are typically expressed on professional antigen-presenting cells but can also be expressed on certain tumor cells.<br> <br> HLA expression significantly influences tumor-immune interactions and, by extension, patient prognosis. While reduced HLA class I expression generally correlates with immune escape and poorer outcomes, the prognostic impact of HLA class II is more context-dependent and may vary by tumor type.<br>
1143-	HMG-CoA	↑	3‐hydroxy-3‐methylglutaryl‐coenzyme A			<b>HMG‐CoA (3‐hydroxy-3‐methylglutaryl‐coenzyme A) </b><br> HMG‐CoA is not a single enzyme but rather a key metabolic intermediate in the mevalonate pathway that underlies cholesterol and isoprenoid biosynthesis. <br> – HMG‐CoA is a pivotal intermediate formed from acetyl‐CoA (via the enzyme HMG‐CoA synthase) that subsequently undergoes reduction (via HMG‐CoA reductase) to produce mevalonate.<br> – The mevalonate pathway supplies cholesterol and other isoprenoids, which are essential for membrane biogenesis, protein prenylation, and other cellular functions that support cell proliferation and survival.<br> – The availability of HMG‐CoA and subsequent metabolites has implications for modifying cell signaling pathways, including those involved in the regulation of cell growth, differentiation, and apoptosis.<br> – Markers of an activated mevalonate pathway (such as increased expression of HMG‐CoA synthase or HMG‐CoA reductase) have been associated with aggressive tumor phenotypes in several cancer types, including breast, prostate, and liver cancers.<br>
1059-	HMGB1	↑	High Mobility Group Box 1			<b>HMGB1</b> is a nuclear protein that plays key roles in DNA architecture and regulation of transcription; however, when released extracellularly it can act as a damage-associated molecular pattern (DAMP), influencing immune responses and affecting tumor progression.<br> <br> Overexpression of HMGB1, particularly when associated with increased extracellular release, is frequently correlated with enhanced tumor aggressiveness, metastasis, and poorer survival across several cancer types including breast, colorectal, lung, ovarian, and pancreatic cancers.<br> • Its critical involvement in inflammation and immune modulation makes HMGB1 an attractive candidate for targeted therapeutic intervention as well as a potential prognostic marker.<br>
1133-	HMGCR	↑	3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)			<b>3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR)</b><br> – HMGCR catalyzes the conversion of HMG-CoA to mevalonate, a critical step in the cholesterol biosynthesis pathway.<br> – Cholesterol is essential for maintaining cell membrane integrity and serves as a precursor for steroid hormones, which can influence tumor growth.<br> <br> – In certain contexts, elevated HMGCR expression has been linked to more aggressive tumor phenotypes, increased proliferation, and, in some cases, poorer overall survival.<br>
1096-	HMTs	↑	Histone methyltransferases (HMTs)			<b>Histone methyltransferases (HMTs)</b> are enzymes that catalyze the addition of methyl groups to histones, leading to chromatin modifications that regulate gene expression. Altered expression and activity of various HMTs have been implicated in cancer initiation, progression, and response to therapy. However, given the diversity of HMT family members (e.g., EZH2, SETDB1, SUV39H1/2, DOT1L, MLL family members), the prognostic associations can vary considerably depending on the specific enzyme and cancer type. <br> <br> – High levels of some HMTs (e.g., EZH2) are often linked to advanced disease stage and poorer survival<br> • Enzyme-Specific Effects: The prognostic value largely depends on which HMT is altered. For instance, while overexpression of EZH2 is commonly a marker of poor prognosis, some HMTs may act as tumor suppressors, and their loss could be associated with aggressive behavior.<br>
1137-	HNE	↑	4-hydroxynonenal (HNE)			<b>HNE</b> is a lipid peroxidation product formed during oxidative stress and is considered both a signaling molecule and a cytotoxic agent depending on its cellular concentration and context.<br> – HNE is generated as a byproduct of the peroxidation of ω-6 polyunsaturated fatty acids.<br> – It serves as a marker of oxidative stress and can modify proteins, lipids, and DNA through covalent adduct formation.<br> <br> • Dual Biological Effects<br> – At low to moderate concentrations, HNE can act as a signaling molecule, modulating pathways involved in cell proliferation, differentiation, and apoptosis.<br> – At higher concentrations, HNE is cytotoxic, causing cellular damage and contributing to cell death through protein dysfunction and DNA damage.<br> – This concentration-dependent activity means that HNE can have both pro-tumorigenic and anti-tumorigenic effects.<br> <br> – Elevated levels of HNE in tissues or biological fluids are frequently used as indicators of oxidative stress within the tumor microenvironment.<br>
146-	HNF1A	↓	HNF1 homeobox A	CGL-Driver Genes	TSG	<b>HNF1A (Hepatocyte Nuclear Factor 1 Alpha)</b> is also known as HNF1 homeobox A. The term "homeobox" refers to a specific DNA sequence that encodes a protein domain known as the homeodomain, which is involved in regulating gene expression during development.<br> HNF1A is a transcription factor that plays a crucial role in the regulation of genes involved in glucose metabolism, liver function, and pancreatic development. While HNF1A is primarily known for its role in diabetes and metabolic disorders, there is emerging evidence suggesting that it may also be involved in cancer biology.<br> HNF1A may act as a tumor suppressor in certain types of cancer, particularly in liver cancer (hepatocellular carcinoma). Loss of HNF1A expression has been associated with poor prognosis in these cases.<br>
388-	hnRNPA1	↑	Heterogeneous nuclear ribonucleoprotein A			<b>Heterogeneous nuclear ribonucleoprotein A/B (hnRNPA/B)</b> is one of the core members of the RNA binding protein (RBP) hnRNPs family, including four main subtypes, A0, A1, A2/B1 and A3, which share the similar structure and functions. <br> hnRNPA1 was highly expressed in gastric cancer tissues, which promote proliferation, migration and EMT of gastric cancer cells. Down-regulation of HNRNPA1 could suppress tumorigenesis by cell cycle arrest or by inducing apoptosis in cancer cells.<br> <br> Oncogenic Potential:<br> hnRNPA1 has been shown to have oncogenic properties in certain contexts, promoting cell proliferation and survival.<br> Its dysregulation can lead to alternative splicing events that contribute to cancer progression and metastasis.<br> <br> Its overexpression is associated with various cancers, including breast, lung, colorectal, and prostate cancers, often correlating with poor prognosis and aggressive tumor behavior. As a potential therapeutic target and biomarker, hnRNPA1 represents an important area of research in oncology.<br>
597-	HO-1	↑	HMOX1			<b>(Also known as Hsp32 and HMOX1)</b><br> HO-1 is the common abbreviation for the protein (heme oxygenase‑1) produced by the HMOX1 gene.<br> HO-1 is an enzyme that plays a crucial role in various cellular processes, including the breakdown of heme, a toxic molecule. Research has shown that HO-1 is involved in the development and progression of cancer.<br> -widely regarded as having antioxidant and cytoprotective effects<br> -The overall activity of HO‑1 helps to reduce the pro‐oxidant load (by degrading free heme, a pro‑oxidant) and to generate molecules (like bilirubin) that can protect cells from oxidative damage<br> <br> Studies have found that HO-1 is overexpressed in various types of cancer, including lung, breast, colon, and prostate cancer. The overexpression of HO-1 in cancer cells can contribute to their survival and proliferation by:<br>   Reducing oxidative stress and inflammation<br>   Promoting angiogenesis (the formation of new blood vessels)<br>   Inhibiting apoptosis (programmed cell death)<br>   Enhancing cell migration and invasion<br> When HO-1 is at a normal level, it mainly exerts an antioxidant effect, and when it is excessively elevated, it causes an accumulation of iron ions.<br> <br> A proper cellular level of HMOX1 plays an antioxidative function to protect cells from ROS toxicity. However, its overexpression has pro-oxidant effects to induce ferroptosis of cells, which is dependent on intracellular iron accumulation and increased ROS content upon excessive activation of HMOX1.<br> <br> -Curcumin   Activates the Nrf2 pathway leading to HO‑1 induction; known for its anti‑inflammatory and antioxidant effects.<br> -Resveratrol  Induces HO‑1 via activation of SIRT1/Nrf2 signaling; exhibits antioxidant and cardioprotective properties.<br> -Quercetin   Activates Nrf2 and related antioxidant pathways; contributes to anti‑oxidative and anti‑inflammatory responses.<br> -EGCG     Promotes HO‑1 expression through activation of the Nrf2/ARE pathway; also exhibits anti‑inflammatory and anticancer properties.<br> -Sulforaphane One of the most potent natural HO‑1 inducers; triggers Nrf2 nuclear translocation and upregulates a battery of phase II detoxifying enzymes.<br> -Luteolin    Induces HO‑1 via Nrf2 activation; may also exert anti‑inflammatory and neuroprotective effects in various cell models.<br> -Apigenin   Has been reported to induce HO‑1 expression partly via the MAPK and Nrf2 pathways; also known for anti‑inflammatory and anticancer activities.<br>
1151-	HO-2	↑	HO-2			<b>Heme oxygenases</b> are enzymes that catalyze the degradation of heme into biliverdin, free iron, and carbon monoxide. There are two main isoforms: HO-1, which is highly inducible under stress conditions, and HO-2, which is constitutively expressed.<br> HO-2 is constitutively expressed in many tissues and is less sensitive to stress-induced upregulation compared to HO-1.<br> It contributes to normal cellular heme turnover, with the resulting products (e.g., biliverdin, bilirubin, and carbon monoxide) having cytoprotective, anti-inflammatory, and anti-apoptotic properties.<br> <br> -Higher constitutive expression of HO-2 has been associated with maintaining cell survival under conditions of oxidative stress, which, in turn, could be linked to more aggressive tumor behavior or resistance to therapy in certain contexts.<br>
1257-	homoC	↑	homocysteine			<b>Homocysteine</b> is a sulfur-containing amino acid produced during the metabolism of methionine. Elevated homocysteine levels and alterations in its metabolic enzymes have been associated with various pathological processes, including oxidative stress, DNA damage, and inflammation.<br> -Elevated plasma homocysteine levels (hyperhomocysteinemia) are a well‐established risk factor for cardiovascular diseases.<br> -Some studies have suggested that high levels of homocysteine might be associated with an increased risk of certain cancers.<br> -Vitamins like folate, B6, and B12 are key regulators of homocysteine metabolism, some research has examined whether supplementation might modulate cancer risk. However, clinical outcomes have been mixed and further research is needed.<br> <br> -Various clinical trials have shown that the oral supplementation of folic acid, B6, and B12 vitamins significantly lowers circulating homocysteine levels.<br>
797-	HR	⇅	Homologous recombination		genes	<b>Homologous recombination (HR)</b> is a type of DNA repair mechanism that plays a crucial role in maintaining genome stability. <br> HR helps to repair DNA double-strand breaks (DSBs) and other types of DNA damage, maintaining genome stability and preventing mutations that can lead to cancer.<br> HR genes include: RAD51, BRCA1, BRCA2, RAD52, RAD54, XRCC2, CRcc3<br>
147-	HRAS	↑	v-Ha-ras Harvey rat sarcoma viral oncogene homolog	CGL-Driver Genes	Oncogene	<b>HRAS</b> (Harvey rat sarcoma viral oncogene homolog) is one of the three main RAS genes (HRAS, KRAS, and NRAS) that encode proteins involved in cell signaling pathways that control cell growth and differentiation. Mutations in HRAS can lead to uncontrolled cell proliferation and are associated with various types of cancer.<br> When mutated, HRAS can become constitutively active, leading to continuous signaling for cell division and survival, contributing to tumorigenesis.<br>
898-	HRI	⇅	Heme-regulated eIF2α kinase			<b>Heme-regulated eIF2α kinase (HRI)</b> is a protein kinase that plays a crucial role in regulating protein synthesis in response to cellular stress, including hypoxia, oxidative stress, and nutrient deprivation. HRI is activated by the depletion of heme, a key component of hemoglobin and other hemoproteins, and phosphorylates the alpha subunit of eukaryotic translation initiation factor 2 (eIF2α), leading to the inhibition of protein synthesis.<br> The heme-regulated eIF2α kinase (HRI) is an Hsp90 client kinase which, upon folding by Hsp90, will activate, or mature, by autophosphorylation when heme is deficient.<br> HRI is part of the eIF2α kinase family, which includes other kinases like PERK, GCN2, and PKR, all of which phosphorylate the eukaryotic initiation factor 2 alpha (eIF2α) to inhibit protein translation.<br>
848-	hs-CRP	↑	High-sensitivity C-reactive protein		biomarker	<b>High-sensitivity C-reactive protein (hs-CRP)</b> is a biomarker that measures inflammation in the body. Research has shown that elevated levels of hs-CRP are associated with an increased risk of various types of cancer.<br> • hs-CRP:<br> + Normal: < 1 mg/L<br> + Elevated: 1-3 mg/L (may indicate chronic inflammation)<br> + High: > 3 mg/L (may indicate increased cardiovascular risk or chronic inflammation)<br>
473-	Hsc70	↑	Heat Shock Cognate Protein 70			<b>Hsc70</b> is critical for cancer cell survival. HSC70 shares some of the structural and functional similarity with HSP70. HSC70 also has different properties compared with HSP70 and other heat shock family members. HSC70 performs its full functions by the cooperation of co-chaperones. It interacts with many other molecules as well and regulates various cellular functions.<br>
1048-	HSD17B4	↑	hydroxysteroid 17-beta dehydrogenase 4			<b>HSD17B4</b> (hydroxysteroid 17-beta dehydrogenase 4) is a multifunctional enzyme predominantly involved in peroxisomal β‑oxidation of fatty acids and steroid metabolism. Its dysregulation has attracted attention in various cancers.<br> Breast Cancer<br> • Expression:<br> – Some studies have observed altered HSD17B4 expression in breast cancer tissues compared to normal tissues. In certain cohorts, overexpression has been noted, which may affect local steroid metabolism and estrogen synthesis.<br> • Prognosis:<br> – Overexpression in some reports has been linked to endocrine resistance and a more aggressive phenotype, suggesting a potential role as a marker of unfavorable prognosis.<br> <br> Hepatocellular Carcinoma (HCC)<br> • Expression:<br> – In liver cancers, HSD17B4 expression may be aberrant. Some studies have reported increased expression compared to non-tumor liver tissues, potentially reflecting metabolic reprogramming in cancer cells.<br> • Prognosis:<br> – Elevated HSD17B4 expression in HCC has been associated in certain reports with poor survival outcomes, suggesting its involvement in tumor metabolism and progression.<br>
455-	HSD3B	↑	HSD3B			<b>Also 3BHS1, 3BH, HSDB3, and HSD3B</b><br> HSD3B refers to 3β-hydroxysteroid dehydrogenase, an enzyme that plays a critical role in steroid hormone biosynthesis. There are several isoforms of this enzyme, with HSD3B1 and HSD3B2 being the most studied. These enzymes catalyze the conversion of pregnenolone to progesterone and the conversion of dehydroepiandrosterone (DHEA) to androstenedione, which are important steps in the synthesis of various steroid hormones.<br> HSD3B1 is a gene that encodes an enzyme involved in steroid hormone biosynthesis and metabolism.<br> <br> HSD3B expression has been observed in various cancers, particularly those that are hormone-dependent, such as breast, prostate, and ovarian cancers.<br> HSD3B is involved in steroid hormone biosynthesis and has been implicated in various cancers, particularly hormone-dependent tumors. Its expression levels may have prognostic significance, and while it is not classified as an oncogene, its role in hormone metabolism can influence cancer progression and treatment response<br>
1072-	HSF1	↑	Heat Shock Factor 1			<b>HSF1</b> is the master regulator of the heat shock response. When cells experience stress (e.g., heat, oxidative stress, hypoxia), HSF1 becomes activated and translocates to the nucleus.<br> – Beyond facilitating the immediate survival response to stress, HSF1 also regulates genes involved in protein folding, degradation, and overall cellular quality control.<br> <br> Oncogenic Functions:<br> – In cancer, HSF1 is frequently hijacked to support malignant progression. It can promote several cancer hallmarks including cell proliferation, survival, invasion, and metastasis.<br> – Elevated HSF1 expression and activity have been observed in various tumor types, including breast, prostate, lung, and colorectal cancers.<br> – Elevated HSF1 expression/activity is generally associated with poor clinical outcomes, aggressive cancer behavior, and therapeutic resistance.<br>
386-	HSP27	↑	Heat shock protein 27		Protein	<b>Heat Shock Protein 27 (Hsp27),</b> also known as HSPB1, is a small heat shock protein that plays a crucial role in cellular stress responses, protein folding, and protection against apoptosis. <br> Hsp27 is involved in various cellular processes, including the stabilization of proteins, regulation of the cytoskeleton, and modulation of signaling pathways.<br> Acts as a protein chaperone and an antioxidant and plays a role in the inhibition of apoptosis and actin cytoskeletal remodeling. Plays a key role in anti-cancer treatment resistance, inhibition of apoptosis and tumor progression. HSP27 is upregulated in many cancers and is associated with a poor prognosis.<br> <br> Expression in Cancers: Hsp27 is often overexpressed in various types of cancers, including breast, prostate, lung, and colorectal cancers. Its expression can be induced by stressors such as heat shock, oxidative stress, and exposure to certain chemotherapeutic agents.<br> Prognostic Implications: The expression levels of Hsp27 have been associated with cancer prognosis. In many studies, high levels of Hsp27 expression correlate with poor prognosis, increased tumor aggressiveness, and resistance to chemotherapy.<br>
148-	HSP70/HSPA5	↑	heat shock proteins 70 kilodalton			<b>Also known as HSPA5</b><br> Enhanced expression of Hsp70 is associated with tumorigenesis for breast cancer, endometrial cancer, gastric cancer, and acute leukemia; with poor prognoses.<br> -These adenosine triphosphatases unfold misfolded or denatured proteins and can keep these proteins in an unfolded, folding-competent state. They also protect nascently translating proteins, promote the cellular or organellar transport of proteins, reduce proteotoxic protein aggregates and serve general housekeeping roles in maintaining protein homeostasis. <br> -HSP70 family of proteins can be thought of as a potent buffering system for cellular stress, either from extrinsic (physiological, viral and environmental) or intrinsic (replicative or oncogenic) stimuli. As such, this family serves a critical survival function in the cell. Not surprisingly, cancer cells rely heavily on this buffering system for survival. The overwhelming majority of human tumors overexpress HSP70 family members, and expression of these proteins is typically a marker for poor prognosis.<br> -HSP70 helps cancer cells survive under stressful conditions, such as hypoxia or nutrient deprivation, by preventing protein misfolding and aggregation. This allows cancer cells to maintain their proliferative capacity.<br> -Tumor Progression: Elevated levels of HSP70 have been associated with tumor progression and metastasis.<br>
491-	HSP72	↑	Heat Shock Protein 72			<b>Also known as HSPA1A</b><br> HSP72, or Heat Shock Protein 72, is a member of the heat shock protein family, which plays a crucial role in cellular stress responses. It is also known as HSPA1A and is involved in protein folding, protection against stress-induced damage, and the regulation of apoptosis (programmed cell death). HSP72 can help cancer cells survive under stressful conditions, such as those found in the tumor microenvironment (e.g., low oxygen, nutrient deprivation). This ability to protect cells from stress can contribute to tumor growth and resistance to therapy.<br> Elevated levels of HSP72 have been associated with resistance to various cancer treatments, including chemotherapy and radiation. Cancer cells that express high levels of HSP72 may be more capable of repairing damage caused by these therapies, leading to treatment failure.<br>
149-	HSP90	↑	HSP90	HalifaxProj(inhibit)		<b>Heat shock protein 90 (Hsp90)</b> is a molecular chaperone that plays a critical role in the proper folding, stabilization, and function of many proteins, including those involved in cell signaling, cell cycle regulation, and stress responses.<br> -Hsp90 interacts with a variety of client proteins that are often mutated or overexpressed in cancer. These include oncogenes (like HER2, BRAF, and AKT) and tumor suppressor proteins (like p53).<br> -Hsp90 is often overexpressed in cancer cells, which can help them survive under stressful conditions, such as those found in the tumor microenvironment. This overexpression is associated with poor prognosis in several types of cancer.<br> -HSPs, particularly HSP90, are known to stabilize many proteins that drive cancer progression (oncoproteins).<br>
1272-	HSPs	↑	Heat shock proteins			<b>Heat shock proteins (HSPs)</b> are a diverse group of molecular chaperones that assist in proper protein folding, stabilization of proteins against aggregation, and protein trafficking. In cancer, HSPs are often overexpressed, which can help tumor cells survive the stressful conditions present in the tumor microenvironment (such as hypoxia, oxidative stress, and nutrient deprivation).<br> <br> -Overexpression: Many cancers exhibit high levels of HSPs compared to their normal tissue counterparts. Overexpression of chaperones like HSP27, HSP70, and HSP90 is common in various tumors.<br>
150-	hTERT	↑	human telomerase reverse transcriptase	HalifaxProj(inhibit)		<b>A key component of the enzyme telomerase,</b> which is responsible for maintaining the length of telomeres at the ends of chromosomes. <br> In most somatic cells, telomerase activity is low or absent, leading to progressive telomere shortening with each cell division, which eventually triggers cellular senescence or apoptosis. many cancer cells exhibit reactivation of telomerase, primarily through the upregulation of hTERT. This reactivation allows cancer cells to maintain their telomere length, enabling them to divide indefinitely and contributing to the immortality characteristic of cancer cells. The expression of hTERT is often associated with various types of cancer, including melanoma, breast cancer, and lung cancer.<br>
1167-	hyperG	↑	hyperglycemia			<b>Hyperglycemia</b> is defined as elevated blood glucose levels and may result from diabetes mellitus, insulin resistance, or stress-induced metabolic changes.<br> <br> – Elevated glucose levels provide abundant energy resources, potentially facilitating rapid tumor cell division and growth.<br> – Some cancers upregulate glucose transporters (such as GLUT1) to utilize the increased availability of glucose.<br> <br> Oxidative Stress and DNA Damage:<br> – Hyperglycemia is associated with the production of reactive oxygen species (ROS) and advanced glycation end-products (AGEs).<br> – Both ROS and AGEs can lead to DNA damage, genomic instability, and alterations in cell signaling pathways that promote tumor progression.<br> <br> – Studies have linked hyperglycemia with increased tumor aggressiveness in several cancer types, including breast, colorectal, and pancreatic cancers.<br> – Patients with hyperglycemia may experience more rapid disease progression and a higher likelihood of metastasis.<br> – In some cases, elevated glucose levels have been associated with chemotherapy resistance and decreased sensitivity to radiation therapy.<br> <br> – Effective control of blood sugar through dietary interventions, medications (e.g., insulin, metformin), and lifestyle modifications may beneficially impact cancer outcomes.<br> – Regular monitoring of blood glucose and hemoglobin A1c (HbA1c) can inform oncologists about potential metabolic challenges during cancer treatment.<br>
151-	Hypoxia	↑	Hypoxia	HalifaxProj(reduce)		<b>Deprived</b> of adequate oxygen supply at the tissue level.<br> Hypoxia, a condition characterized by insufficient oxygen levels in tissues.<br> Cancer cells can adapt to hypoxic conditions through various mechanisms. They may activate hypoxia-inducible factors (HIFs), which are transcription factors that help cells respond to low oxygen levels. HIFs promote the expression of genes involved in angiogenesis (formation of new blood vessels), metabolism, and survival.<br> Tumors with high levels of hypoxia may be more aggressive and less responsive to treatment.<br>
979-	IAP1	↑	cIAP1, cellular Inhibitor of Apoptosis Protein 1			<b>IAP1</b> (cIAP1, encoded by the gene BIRC2) is a member of the Inhibitor of Apoptosis (IAP) protein family.<br> • IAP proteins generally function by binding and inhibiting components of the cell death machinery, thereby promoting cell survival.<br> • Beyond their role in directly suppressing apoptosis, IAP proteins (including IAP1) are involved in regulating other signaling pathways—such as NF-κB—that can influence inflammation, immune responses, and cellular proliferation.<br> <br> Overexpression of IAP proteins, including IAP1, has been observed in various tumor types. – High IAP1 levels can help tumor cells evade apoptosis (programmed cell death), contributing to tumor growth and progression.<br> • IAP1 may also influence the tumor microenvironment by modulating pro-survival and inflammatory signals.<br>
980-	IAP2	↑	cIAP2, cellular Inhibitor of Apoptosis Protein 2			<b>IAP2</b> (cellular Inhibitor of Apoptosis Protein 2) is a member of the Inhibitor of Apoptosis (IAP) protein family.<br> • Like its family members, IAP2 functions to regulate cell survival primarily by inhibiting caspases and other components of the apoptotic machinery.<br> • IAP2 also influences signaling pathways, such as NF-κB, which affects inflammatory responses, cell proliferation, and survival.<br> <br> • Overexpression or dysregulation of IAP2 has been observed in various malignancies.<br> – Elevated IAP2 levels can help tumor cells evade apoptosis, promoting tumor growth and survival.<br> – IAP2, similar to IAP1, may contribute to resistance against chemotherapies and targeted therapies by blocking cell death pathways.<br>
877-	ICAD	⇅	inhibitor of caspase-activated DNase			<b>ICAD</b> (inhibitor of caspase-activated DNase, also known as DFFA) <br> ICAD is the physiological inhibitor of CAD, the nuclease responsible for executing DNA fragmentation during apoptosis.<br> • Caspase-mediated cleavage of ICAD is a key regulatory step that unleashes CAD activity during apoptosis.<br> <br> Its dysregulation (either up‐ or down‐regulation) has been linked to altered apoptotic responses, genomic instability, and ultimately clinical outcomes.<br> Either overexpression or underexpression can disrupt this balance:<br> ▪ Overexpression may blunt the full execution of apoptosis in response to stresses (e.g., chemotherapy).<br> ▪ Underexpression may lead to unscheduled or incomplete apoptosis, which in some scenarios might paradoxically fuel genomic instability.<br>
419-	ICAM-1	↑	Intercellular Adhesion Molecule 1			<b>ICAM-1</b> also known as CD54 is a protein that in humans is encoded by the ICAM1 gene. ICAM-1 is an important regulator of cell–cell interactions and recent studies have shown that it promotes malignancy in several carcinomas.<br> Intercellular Adhesion Molecule 1 (ICAM-1) is a cell surface glycoprotein that plays a critical role in the immune response by facilitating the adhesion of leukocytes to endothelial cells. It is part of the immunoglobulin superfamily and is involved in various cellular processes, including inflammation, immune response, and tumor progression.<br> Expression in Cancers: ICAM-1 is often overexpressed in various types of cancers, including breast, lung, colorectal, and melanoma. Its expression can be induced by pro-inflammatory cytokines, growth factors, and other stimuli present in the tumor microenvironment.<br> Prognostic Implications: The expression levels of ICAM-1 have been associated with cancer prognosis. In some studies, high levels of ICAM-1 expression correlate with poor prognosis, increased tumor aggressiveness, and a higher likelihood of metastasis. <br> <br> ICAM-1 is an adhesion molecule that is often overexpressed in various cancers and is associated with poor prognosis and increased metastatic potential.<br>
1080-	ICD	↓	immunogenic cell death (ICD)		type of cell death	<b>Immunogenic cell death (ICD)</b> is a form of regulated cell death that stimulates the immune system against dying cells.<br> ICD is characterized by the release or exposure of specific damage‐associated molecular patterns (DAMPs) that function as “danger signals.” Key DAMPs (or ICD markers) include:<br> • Calreticulin (CRT) exposure<br> • ATP release<br> • High mobility group box 1 protein (HMGB1) release<br> • Heat shock proteins (such as HSP70 and HSP90)<br> • Type I interferon (IFN) responses (indirectly involved through downstream signaling)<br> <br> Higher expression/exposure of ICD markers such as calreticulin, ATP, extracellular HMGB1 (with favorable redox states), HSP70/90 when released, and type I IFN responses are generally associated with enhanced antitumor immunity and improved prognosis in several cancer types.<br>
513-	Id1	↑	Inhibitor of DNA binding 1(Inhibitor of Differentiation 1)		protein	<b>Inhibitor of DNA binding 1(Inhibitor of Differentiation 1)</b><br> The inhibitor of DNA binding (Id) proteins are regulators of cell cycle and cell differentiation. Of all Id family proteins, Id1 is mostly linked to tumorigenesis, cellular senescence as well as cell proliferation and survival. Id1 is a stem cell-like gene more than a classical oncogene. Id1 is overexpressed in numerous types of cancers and exerts its promotion effect to these tumors through different pathways.<br>
152-	IDH1	↑	isocitrate dehydrogenase 1 (NADP+), soluble	CGL-Driver Genes	Oncogene	<b>An enzyme</b> that plays a crucial role in the citric acid cycle (Krebs cycle), which is essential for cellular metabolism. Mutations in the IDH1 gene have been implicated in various types of cancer, particularly gliomas and acute myeloid leukemia (AML).<br> Expression in Cancers: IDH1 is expressed in various tissues, and its expression can be altered in cancer. Mutations in the IDH1 gene, particularly the R132H mutation, are commonly found in certain types of tumors, including gliomas and secondary glioblastomas, as well as in a subset of acute myeloid leukemia cases.<br> Prognostic Implications: The presence of IDH1 mutations is associated with distinct clinical outcomes. In gliomas, IDH1 mutations are generally linked to a better prognosis compared to wild-type IDH1. Patients with IDH1-mutant gliomas often have longer survival rates and respond differently to treatment. In AML, IDH1 mutations can also influence prognosis, with some studies suggesting that they may be associated with a favorable response to certain therapies.<br> Oncogenic Potential: Mutant IDH1 is considered an oncogene due to its role in altering cellular metabolism. The R132H mutation leads to a neomorphic enzyme activity that converts alpha-ketoglutarate to 2-hydroxyglutarate (2-HG), an oncometabolite that can inhibit various α-ketoglutarate-dependent dioxygenases, including those involved in DNA and histone demethylation. This alteration in metabolism and epigenetic regulation contributes to tumorigenesis and the development of cancer.<br> <br> IDH1 (Isocitrate Dehydrogenase 1) is not classified as a traditional oncogene. Instead, it is considered a mutated metabolic enzyme that can contribute to oncogenesis when mutated. Here’s a more detailed explanation:<br>
153-	IDH2	↑	isocitrate dehydrogenase 2 (NADP+), mitochondrial	CGL-Driver Genes	Oncogene	<b>An enzyme</b> that plays a crucial role in the citric acid cycle (Krebs cycle), which is essential for cellular metabolism. Mutations in the IDH2 gene have been implicated in various types of cancer, particularly in hematological malignancies such as acute myeloid leukemia (AML) and certain brain tumors like gliomas.<br> IDH2 mutations often lead to a gain of function, resulting in the production of 2-hydroxyglutarate (2-HG), an oncometabolite. Elevated levels of 2-HG can disrupt normal cellular processes, including DNA and histone methylation, leading to altered gene expression and promoting tumorigenesis.<br> <br> IDH2 (Isocitrate Dehydrogenase 2) is another enzyme involved in cellular metabolism, similar to IDH1. It is primarily located in the mitochondria and plays a role in the citric acid cycle. Mutations in the IDH2 gene are associated with various cancers, particularly acute myeloid leukemia (AML) and some solid tumors. <br>
154-	IDO	↑	indoleamine 2,3-dioxygenase	HalifaxProj(inhibit)		<b>An enzyme</b> that plays a significant role in the metabolism of the amino acid tryptophan. It is involved in the kynurenine pathway, which leads to the production of several metabolites that can influence immune responses and have implications in cancer.<br> IDO has garnered attention for its role in immune evasion. Many tumors express IDO, which can lead to local depletion of tryptophan and accumulation of kynurenine and other metabolites. This can suppress T-cell activity and promote the differentiation of regulatory T cells, thereby helping tumors evade the immune system.<br>
975-	IDO1	↑	indoleamine 2, 3-dioxygenase 1			<b>IDO1 (Indoleamine 2,3-dioxygenase 1)</b> is an enzyme involved in the catabolism of the essential amino acid tryptophan through the kynurenine pathway. Its activity can modulate the tumor immune microenvironment, and its expression has been associated with immune tolerance in various cancers.<br> <br> – IDO1 is frequently overexpressed in a wide range of cancers, including melanoma, lung, breast, colorectal, and ovarian cancers.<br> – Elevated IDO1 expression in tumors is often found both in tumor cells and in immune cells within the tumor microenvironment.<br> – Inhibitors of IDO1 aim to restore tryptophan levels in the tumor microenvironment and reinvigorate T-cell mediated anti-tumor responses.<br> <br> IDO1 inhibitory effects:<br> -Epigallocatechin Gallate (EGCG)<br> -Curcumin<br> -Resveratrol<br> -Berberine<br> -4‑phenylimidazole (research drug, small molecule)<br> <br> IDO1 is an immunomodulatory enzyme that catabolizes tryptophan into kynurenine and related metabolites, thereby influencing the local immune environment.<br> Its expression is found in various cell types, including tumor cells, antigen-presenting cells, and stromal cells.<br> • IDO1 activity results in local tryptophan depletion and accumulation of immunosuppressive metabolites, which can impair T-cell function and promote regulatory T-cell (Treg) generation.<br> • IDO1 is largely viewed as a facilitator of tumor immune escape through its immunosuppressive actions, including the depletion of tryptophan and accumulation of kynurenine.<br> <br> • Increased expression of IDO1 has been consistently linked to poorer outcomes across various cancer types.<br> <br> • Although not oncogenic in itself, IDO1 enables a protumoral microenvironment by dampening anti-tumor immune responses.<br>
442-	IFN-γ	?	Interferon-γ			<b>Plays a key role</b> in activation of cellular immunity and subsequently, stimulation of antitumor immune-response. Based on its cytostatic, pro-apoptotic and antiproliferative functions, IFN-γ is considered potentially useful for adjuvant immunotherapy for different types of cancer.<br> Moreover, it IFN-γ may inhibit angiogenesis in tumor tissue, induce regulatory T-cell apoptosis, and/or stimulate the activity of M1 proinflammatory macrophages to overcome tumor progression.<br> However, the current understanding of the roles of IFN-γ in the tumor microenvironment (TME) may be misleading in terms of its clinical application.<br> <br> IFN-γ is often expressed in the tumor microenvironment, particularly in response to immune cell infiltration. Its expression can be influenced by the presence of tumor-infiltrating lymphocytes (TILs) and other immune cells.<br> High levels of IFN-γ are typically associated with a Th1 immune response, which is generally considered beneficial for anti-tumor immunity.<br> <br> Tumor Suppression:<br> In many cases, IFN-γ has tumor-suppressive effects, as it can inhibit tumor cell proliferation and induce apoptosis in certain cancer types.<br>
415-	IGF-1	↑	insulin-like growth factor-1			<b>Higher blood levels of IGF-1,</b> a growth factor, are linked to increased risk of several types of cancer, including thyroid, melanoma and myeloma. IGF-1 is what some call "a growth-promoter" because it has been shown to promote the growth of cancer cells.<br> <a href="https://pubmed.ncbi.nlm.nih.gov/22520978/"> The IGF-1 signaling pathway promotes cancer progression;</a> its downregulation is associated with lowered risk.<br> <a htref="https://pubmed.ncbi.nlm.nih.gov/22520978/">
155-	IGF-1R	↑	insulin-like growth factor-1 receptor	HalifaxProj(inhibit)		<b>Also IGF1R</b><br> A link between elevated IGF levels and the development of solid tumors, such as breast, colon, and prostate cancer. Gene amplification of IGF1R, which encodes insulin-like growth factor 1 receptor, is a frequent event across cancer types. Upregulation of IGF1R protein expression in tumor samples and serum in NSCLC patients. Upregulation of IGF-IR signaling can help cancer cells resist anoikis by inhibiting p53 and p21 activation.<br> Many cancers, including breast, prostate, lung, and colorectal cancers, have been found to exhibit overexpression of IGF-1R. This overexpression can contribute to increased cell proliferation and survival, promoting tumor growth.<br>
416-	IGF-2	↑	Insulin-like growth factor 2		Oncogene	<b>Insulin-like Growth Factor 2 (IGF-2)</b> is a protein that plays a significant role in growth and development, particularly during fetal development. It is part of the insulin-like growth factor (IGF) family, which includes IGF-1 and IGF-2, and is involved in cellular growth, differentiation, and survival. <br> -IGF2 is a mitogenic polypeptide that is abundantly expressed in the brain, especially in the cortex and hippocampus, and is required for memory consolidation and enhancement.<br> <br> IGF-2 is often overexpressed in various human cancers because the dysregulation of the differentially methylated region (DMR) on the maternal chromosome causes loss of imprinting (LOI).<br> <br> Oncogenic Potential:<br> IGF-2 is considered an oncogene due to its role in promoting cell proliferation and survival. It activates signaling pathways such as the PI3K/Akt and MAPK pathways, which are critical for cell growth and survival.<br> The overexpression of IGF-2 can lead to increased tumor cell proliferation, invasion, and metastasis.<br> High levels of IGF-2 expression are often associated with a poor prognosis in various cancers. <br>
1189-	IGFBP1	↓	Insulin-like Growth Factor Binding Protein 1			<b>IGFBP1</b> is one of several binding proteins that modulate IGF (insulin-like growth factor) availability and signaling, which can affect cell proliferation, apoptosis, and cellular metabolism.<br> <br> – In some cohorts, higher circulating or tissue levels of IGFBP1 have been associated with a less aggressive disease phenotype and better overall survival.<br> <br> – Conversely, in other studies, low IGFBP1 levels have been linked with a more advanced disease state, suggesting that IGFBP1 may serve as an indicator of preserved liver function or a less aggressive tumor biology.<br>
417-	IGFBP3	↓	Insulin-Like Growth Factor Binding Protein-3			<b>One of the six members of the IGFBP family,</b> is a key protein in the IGF pathway. IGFBP-3 is the most abundant in the blood circulation. Prostate specific antigen (PSA), which is frequently used as a clinical tumor marker for prostate cancer, cleaves IGFBP-3.<br> <br> Tumor Types:<br> IGFBP-3 expression can vary significantly across different cancer types. It is often downregulated in several malignancies, including breast cancer, prostate cancer, colorectal cancer, and lung cancer.<br> In some cases, low levels of IGFBP-3 are associated with tumor progression and poor clinical outcomes.<br> <br> Tumor Suppressor Functions:<br> IGFBP-3 is often considered a tumor suppressor due to its ability to inhibit the actions of IGF-1 and IGF-2, which promote cell proliferation and survival. By binding to IGFs, IGFBP-3 can prevent their interaction with IGF receptors, thereby inhibiting their mitogenic effects.<br> <br> High levels of IGFBP-3 are generally associated with a favorable prognosis in several cancers. For example, elevated IGFBP-3 levels in breast cancer and prostate cancer have been linked to better survival outcomes.<br> Conversely, low levels of IGFBP-3 are often associated with aggressive tumor behavior and poorer prognosis.<br>
1152-	IGFBP7	↓	Insulin-like Growth Factor Binding Protein 7			<b>Insulin-like Growth Factor Binding Protein 7 (IGFBP7)</b> is a secreted protein that modulates the actions of insulin-like growth factors (IGFs) and has been implicated in tumorigenesis, angiogenesis, cellular senescence, and apoptosis. <br> <br> - Reduced expression of IGFBP7 has been associated with tumor progression, whereas in some settings, increased IGFBP7 levels may correlate with an adverse tumor microenvironment or resistance to apoptosis.<br> - In cancers such as colorectal and thyroid cancer, low IGFBP7 expression has been linked to poorer survival rates and more aggressive disease, supporting a tumor-suppressive role.<br> <br> Overall, many studies tend to view IGFBP7 as a marker of better prognosis when expressed at normal or high levels, particularly in cases where it enforces cell cycle arrest or senescence.<br>
827-	IGFR	↑	Insulin-like Growth Factor Receptor		Oncogene	<b>IGFR (Insulin-like Growth Factor Receptor)</b> is a protein that plays a crucial role in cell growth and division. It is a receptor tyrosine kinase that is activated by its ligands, IGF-1 (Insulin-like Growth Factor 1) and IGF-2.<br> IGFR is typically overexpressed and associated with poorer prognosis.<br> IGF-1R is often overexpressed in several types of cancers, including breast cancer, prostate cancer, colorectal cancer, lung cancer, and sarcomas. Its expression can vary significantly depending on the tumor type and stage.<br> High levels of IGF-1R expression are frequently associated with aggressive tumor behavior and poor prognosis.<br> IGF-1R is considered an oncogene due to its role in promoting cell proliferation, survival, and metastasis. Activation of IGF-1R leads to the activation of several downstream signaling pathways, including the PI3K/Akt and MAPK pathways, which are critical for cell growth and survival.<br>
1156-	Igs	⇅	immunoglobulins (IgG and IgM)			<b>Immunoglobulins,</b> particularly IgG and IgM, are traditionally recognized as components of the adaptive immune response; however, they have also been observed to be expressed by certain tumor cells or to play roles in the tumor microenvironment.<br> <br> Immunoglobulins (Igs) are antibodies that mediate humoral immunity. IgM typically represents the initial antibody response to antigens, while IgG is involved in long-term immunity and immunological memory.<br> <br> IgG and IgM are critical players in the immune response, and their presence in tumors can reflect either an active anti-tumor immune response or, in some cases, aberrant expression by tumor cells that may contribute to malignancy.<br> A high density of immune cells producing these antibodies generally correlates with improved prognosis, reflecting an effective immune reaction against the tumor.<br>
1089-	Ikaros	↓	Ikaros			<b>Karos</b> is a zinc finger transcription factor encoded by the IKZF1 gene. It is primarily known for its important roles in:<br>   Hematopoiesis and lymphoid lineage development.<br>   Regulation of gene expression during immune cell differentiation.<br>   Chromatin remodeling and modulation of key signaling pathways in the immune system.<br> Because of its central role in lymphocyte development, Ikaros has been studied extensively in the context of hematological malignancies.<br> <br> In a significant subset of B-cell ALL, particularly those with high-risk features, genomic alterations in IKZF1 are frequently observed. These genetic abnormalities often lead to reduced or dysfunctional Ikaros protein.<br> In ALL, particularly pediatric and adult cases, IKZF1 deletions or mutations are associated with a poor prognosis. This is reflected in shorter event-free survival, higher relapse rates, and overall poorer clinical outcomes.<br>
156-	IKKα	↑	IκB kinase alpha)			<b>Expression of genes</b> involved in nuclear factor (NF)-kappaB activation (NF-κB, IKKα) IKKα (IκB kinase alpha) is a critical component of the NF-κB signaling pathway, which plays a significant role in regulating immune responses, inflammation, and cell survival.<br> The NF-κB pathway, activated by IKKα, can lead to the production of pro-Inhibitors of the NF-κB pathway, including those targeting IKKα, are being investigated for their potential to treat various cancers.inflammatory cytokines that may create a tumor-promoting microenvironment.<br>
365-	IL-1	↑	Interleukin-1			<b>Interleukin-1 (IL-1)</b> has long been known to be a key mediator of immunity and inflammation. Its dysregulation has been implicated in recent years in tumorigenesis and tumor progression, and its upregulation is thought to be associated with many tumors.<br> <br> Interleukin-1 (IL-1) is a pro-inflammatory cytokine that plays a crucial role in the immune response and inflammation. It exists in two main forms: IL-1α and IL-1β, both of which are produced by various cell types, including macrophages, monocytes, and dendritic cells. IL-1 is involved in a wide range of biological processes, including cell proliferation, differentiation, and apoptosis.<br> <br> IL-1 is often overexpressed in various cancers, including breast cancer, colorectal cancer, lung cancer, and melanoma. Its expression can be influenced by the tumor microenvironment and the presence of inflammatory cells.<br> Elevated levels of IL-1 are frequently associated with tumor progression and metastasis.<br> <br> IL-1 is considered a pro-tumorigenic cytokine in many contexts. It can promote tumor growth by enhancing cell proliferation, survival, and angiogenesis. IL-1β, in particular, has been shown to stimulate the proliferation of cancer cells and promote the formation of new blood vessels (angiogenesis).<br>
562-	IL-10	↑	Interleukin-10			<b>IL-10</b> is a multifaceted immune-suppressive cytokine and possesses immune-regulatory and angiogenic functions. <br> It primarily acts as an anti-inflammatory cytokine, protecting the body from an uncontrolled immune response, mostly through the Jak1/Tyk2 and STAT3 signaling pathway. On the other hand, IL-10 can also have immunostimulating functions under certain conditions.<br> The role of IL-10 in tumor pathogenesis is currently highly controversial, with some findings showing that IL-10 promotes tumor development and angiogenesis, while others supporting that it inhibits tumor growth and metastasis.<br> <br> IL-10 is often expressed in various cancers, including breast cancer, colorectal cancer, melanoma, and lymphoma. Its expression can vary significantly depending on the tumor type and the immune context.<br> Elevated levels of IL-10 are frequently associated with the presence of tumor-infiltrating immune cells, particularly Tregs and M2 macrophages.<br>
157-	IL-12	↓	Interleukin-12	HalifaxProj(induce)		<b>IL-12,</b> an antitumor cytokine is considered to be a promising cytokine for enhancing an antitumor immune response.<br> Interleukin-12 (IL-12) is a cytokine that plays a crucial role in the immune response, particularly in the activation of T cells and natural killer (NK) cells. It is produced by various immune cells, including macrophages and dendritic cells, and is known for its ability to promote the differentiation of T cells into a type that can effectively combat cancer cells.<br> <br> IL-12 is often expressed in various cancers, including melanoma, renal cell carcinoma, breast cancer, and colorectal cancer. Its expression can vary depending on the tumor type and the immune context.<br> Tumor-infiltrating immune cells, particularly activated macrophages and dendritic cells, are significant sources of IL-12 in the tumor microenvironment.<br> <br> IL-12 is primarily known for its role in promoting anti-tumor immunity. It enhances the differentiation of naive T cells into T helper 1 (Th1) cells, which produce pro-inflammatory cytokines and support cytotoxic T cell responses.<br> IL-12 also stimulates the activity of NK cells, enhancing their ability to kill tumor cells and produce additional cytokines, such as interferon-gamma (IFN-γ), which further promotes anti-tumor immunity.<br> <br> Low levels of IL-12 in the tumor microenvironment are often associated with poor anti-tumor immune responses and can correlate with worse clinical outcomes. In such cases, strategies to enhance IL-12 production or signaling may be beneficial for improving anti-tumor immunity.<br>
540-	IL-17	↑	Interleukin-17			<b>Also known as IL-17A.</b><br> Interleukin-17A is a protein that in humans is encoded by the IL17A gene.<br> Higher levels of serum IL-17 are associated with poor prognosis for a variety of solid tumors in cancer patients.<br>
369-	IL-18	↑	Interleukin 18			<b>High levels of IL-18</b> production may play a major role in the growth and metastasis of renal cancer. Higher expression of IL-18 is detected in various cancer cells.<br> <br> IL-18 is often expressed in various cancers, including melanoma, colorectal cancer, breast cancer, and gastric cancer. Its expression can vary depending on the tumor type and the immune context. Elevated levels of IL-18 are frequently associated with the presence of tumor-infiltrating immune cells and can be produced by both immune and tumor cells.<br> <br> High levels of IL-18 expression are often associated with a favorable prognosis in various cancers. Elevated IL-18 levels in the tumor microenvironment can correlate with increased immune cell infiltration and better overall survival.<br>
977-	IL-1α	↑	interleukin-1 alpha			<b>The term "IL-1" </b>is often used as an umbrella term for the interleukin-1 family, which includes multiple cytokines. The two best-known members are IL-1α and IL-1β.<br> L-1α: Often expressed as a precursor that is biologically active even before processing; it can be active in its intracellular form and when expressed on the cell surface.<br> IL-1α is typically associated with cell damage and tends to act more locally.<br> <br> High IL-1α levels have been detected in a number of tumor cells and have been associated with enhanced tumor invasion and metastasis in several settings.<br>
978-	IL-1β	↑	interleukin-1 beta			<b>The term "IL-1"</b> is often used as an umbrella term for the interleukin-1 family, which includes multiple cytokines. The two best-known members are IL-1α and IL-1β.<br> IL-1β is secreted from cells and plays a major systemic role in inflammation. It is a crucial mediator in the inflammatory response and is involved in the fever response, activation of endothelial cells, and leukocyte recruitment.<br> Its increased expression is commonly linked to:<br>   – Promotion of a pro-inflammatory microenvironment that supports tumor growth.<br>   – Enhanced angiogenesis, invasion, and metastasis.<br>   – Recruitment of myeloid cells that may further suppress antitumor immunity.<br> <br> High expression of either tends to be associated with a more aggressive phenotype and worse prognosis in many cancer types.<br>
366-	IL-2	⇅	Interleukin-2			<b>The cytokine interleukin-2 (IL-2)</b> can stimulate both effector immune cells and regulatory T (Treg) cells.<br> <br> IL-2 is often expressed in various cancers, including melanoma, renal cell carcinoma, and certain hematological malignancies. Its expression can vary depending on the tumor type and the immune context.<br> Tumor-infiltrating lymphocytes (TILs), particularly activated T cells, are significant sources of IL-2 in the tumor microenvironment.<br> <br> IL-2 is primarily known for its role in promoting anti-tumor immunity. It stimulates the proliferation and activation of T cells, enhancing their ability to recognize and kill tumor cells.<br>
541-	IL-22	↑	Interleukin-22			<b>IL-22</b> has also been identified as a cancer-promoting cytokine since deregulation of the IL-22-IL-22R1 system is linked to different cancer entities including lung, breast, gastric, pancreatic and colon cancers.<br> <br> IL-22 is often expressed in various cancers, including colorectal cancer, breast cancer, liver cancer, and lung cancer. Its expression can vary depending on the tumor type and the immune context. Elevated levels of IL-22 are frequently associated with the presence of tumor-infiltrating immune cells and can be produced by both immune and tumor cells.<br>
543-	IL-23	↑	Interleukin 23			<b>A heterodimeric cytokine</b> composed of an IL-12B subunit and an IL-23A subunit. IL-23 is part of the IL-12 family of cytokines.<br> IL-23 is an inflammatory cytokine. IL-23 is overexpressed in a number of cancer types.<br>
542-	IL-28	↑	Interleukin-28			<b>Interleukin-28 (IL-28),</b> also known as IL-28A or IL-28B, is a member of the type III interferon family, which also includes IL-29. These cytokines play a role in the immune response, particularly in antiviral defense and the regulation of immune cell activity. IL-28 is produced by various cell types, including macrophages, dendritic cells, and epithelial cells, in response to viral infections and other stimuli.<br> A cytokine that comes in two isoforms, IL-28A and IL-28B, and plays a role in immune defense against viruses<br> <br> IL-28 expression has been observed in various cancers, including hepatocellular carcinoma, colorectal cancer, and breast cancer. However, research on IL-28 in cancer is still relatively limited compared to other cytokines.<br> The expression of IL-28 can vary depending on the tumor type and the immune context, and it may be influenced by the presence of viral infections or inflammatory signals.<br> <br> The prognostic significance of IL-28 in cancer is not yet fully established and may vary depending on the tumor type and the immune context. <br>
630-	IL-33	↑	Interleukin-33			<b>IL-33 (Interleukin-33)</b> is a cytokine that plays a crucial role in the regulation of immune responses.<br> IL-33 has both pro-tumor and anti-tumor effects, depending on the type of cancer and the specific microenvironment.<br> IL-33 is expressed in various cancers, including breast cancer, colorectal cancer, lung cancer, and gastric cancer. Its expression can vary significantly depending on the tumor type and the immune context.<br> Elevated levels of IL-33 are often associated with the presence of tumor-infiltrating immune cells and can be produced by both immune and tumor cells.<br> <br> IL-33 is often considered a pro-tumorigenic cytokine. It can promote tumor growth and survival by enhancing the proliferation and survival of cancer cells. IL-33 can activate signaling pathways such as the NF-κB and MAPK pathways, which are associated with cell proliferation and survival.<br>
561-	IL-4	↑	interleukin 4			<b>A cytokine</b> that regulates humoral and adaptive immunity, and is involved in allergies and regulates inflammation.<br> IL-4 produced by cancer cells promotes resistance to immune checkpoint blockade (ICB). The close correlation between interleukin-4 (IL-4) and tumor progression has been observed in plenty of studies.<br> <br> IL-4 is expressed in various cancers, including breast cancer, lung cancer, colorectal cancer, and hematological malignancies. Its expression can vary depending on the tumor type and the immune context.<br> Elevated levels of IL-4 are often associated with the presence of tumor-infiltrating immune cells, particularly Th2 cells and other immune cells that produce IL-4.<br> IL-4 is often considered a pro-tumorigenic cytokine. It can promote tumor growth and survival by enhancing the proliferation and survival of cancer cells. IL-4 can activate signaling pathways such as the STAT6 pathway, which is associated with cell proliferation and survival.<br> In some cancers, IL-4 can also promote angiogenesis, the formation of new blood vessels, which is critical for tumor growth and metastasis.<br>
367-	IL-5	⇅	Interleukin-5			<b>Interleukin-5 (IL-5)</b> is a cytokine that is primarily produced by activated CD4+ helper T cells, mast cells, and eosinophils. It is responsible for stimulating the functions of eosinophils, which are a type of white blood cell.<br> <br> Protumorigenic Role: IL-5 can promote eosinophil survival and activation, which may contribute to tumor progression in certain cancers by enhancing inflammation and tissue remodeling.<br> Antitumorigenic Role: Conversely, in some settings, eosinophils activated by IL-5 may exert antitumor effects, highlighting the dual role of IL-5 in cancer.<br>
158-	IL-6	↑	Interleukin-6	HalifaxProj(inhibit)		<b>Interleukin-6 (IL-6)</b> is a cytokine that plays a significant role in inflammation and the immune response. It is produced by various cell types, including T cells, B cells, macrophages, and fibroblasts. <br> IL-6 can promote tumor cell proliferation and survival. Many cancer cells produce IL-6, which can create an autocrine loop that supports their growth.<br>
368-	IL-8	↑	Interleukin-8			<b>Interleukin-8 (IL-8),</b> also known as CXCL8, is a chemokine primarily involved in the recruitment and activation of neutrophils. Its role in cancer is significant, as it can influence tumor growth, metastasis, and the tumor microenvironment. <br> IL-8 is a chemokine frequently produced in the tumor microenvironment by human malignant cells. IL-8 plays key roles in the immunobiology of human malignancies and resistance to treatments. Circulating IL-8 concentration reflects tumor burden.<br> <br> In many cancers have elevated levels of IL-8 and are associated with increased tumor aggressiveness, metastasis, and poorer overall survival. Elevated IL-8 often correlates with a more inflammatory tumor microenvironment, which can facilitate tumor progression.<br>
755-	IL-9	⇅	Interleukin-9		cytokine	<b>IL-9 (Interleukin-9)</b> is a cytokine. IL-9 is primarily produced by T helper 9 (Th9) cells, a subset of CD4+ T cells.<br> <br> IL-9's role in cancer including:<br> • Promotion of cell proliferation and survival<br> • Inhibition of apoptosis (programmed cell death)<br> • Enhancement of angiogenesis (formation of new blood vessels)<br> • Modulation of the tumor microenvironment<br> <br> IL-9 has also been shown to have anti-tumor effects in certain contexts, such as:<br> • Induction of anti-tumor immune responses<br> • Inhibition of tumor growth and metastasis<br>
1026-	IM	↑	interstitial markers			<b>Interstitial markers</b> are proteins expressed primarily by components of the tumor stroma (the supportive and reactive tissue surrounding tumor cells).<br> They are often used to identify fibroblasts, myofibroblasts, and other stromal cells actively participating in the tumor microenvironment.<br> <br> Common interstitial markers include vimentin, α-smooth muscle actin (α-SMA), fibroblast activation protein (FAP), and platelet-derived growth factor receptor beta (PDGFR-β).<br> <br> Interstitial markers, expressed by the tumor stroma (including proteins such as vimentin, α-SMA, FAP, and PDGFR-β), play important roles in defining the tumor microenvironment. Their increased expression often correlates with a reactive stroma that promotes tumor invasion, metastasis, and therapeutic resistance.<br>
410-	IMPDH1	↑	inosine monophosphate dehydrogenase 1			<b>Upregulation of IMPDH1</b> has been linked to uncontrolled cell proliferation.<br> <br> Many cancers have high levels of IMPDH1 and are associated with increased tumor proliferation, aggressiveness, and poorer overall survival. Its expression often correlates with a more aggressive tumor phenotype.<br>
411-	IMPDH2	↑	inosine monophosphate dehydrogenase 2			<b>IMPDH2</b> promotes colorectal cancer progression through activation of the PI3K/AKT/mTOR and PI3K/AKT/FOXO1 signaling pathways. IMPDH2 expression has been found to be vastly dysregulated in several cancer types, promoting pro-tumorigenic phenotypes and leading to an elevated IMPDH2/IMPDH1 ratio.<br> <br> Many cancers have high levels of IMPDH2 and is associated with increased tumor proliferation, aggressiveness, and poorer overall survival. Its expression often correlates with a more aggressive tumor phenotype.<br>
1032-	importin α/β	↑	importin α/β (karyopherin α and β families)			The importin system, principally composed of importin α and importin β, is a key mediator of nuclear import. Importin α acts as an adaptor that recognizes classical nuclear localization signals (NLS) on cargo proteins, while importin β interacts with the nuclear pore complex to facilitate import into the nucleus. Importin α and β are central mediators of nuclear import, regulating the localization and function of proteins critical for cell proliferation, survival, and DNA repair. In cancer, dysregulation of importin α/β expression or activity can facilitate oncogenic signaling by altering the nuclear transport of growth-promoting or survival factors. Various cancers—including breast, prostate, colorectal, NSCLC, and certain hematologic malignancies—have shown altered importin expression patterns that are often associated with increased tumor aggressiveness and poorer prognostic outcomes. Recent research is exploring inhibitors that target the importin β pathway. Such inhibitors aim to disrupt the nuclear import of oncogenic signals, thereby sensitizing cancer cells to other treatments.
1241-	Inf	↑	Infection			An infection occurs when a microorganism—such as a bacterium, virus, fungus, or parasite—enters the body, establishes itself, and begins to multiply. Oncogenic Viruses and Chronic Infections: Certain viruses are known as oncogenic (cancer-causing) viruses. For example: -Human Papillomavirus (HPV): Certain strains of HPV can lead to cervical cancer, as well as other cancers such as oropharyngeal and anal cancers. -Hepatitis B Virus (HBV) and Hepatitis C Virus (HCV): These viruses can cause chronic liver infections that may progress to liver cirrhosis and ultimately hepatocellular carcinoma (liver cancer). -Epstein-Barr Virus (EBV): This virus is linked to several cancers, including Hodgkin lymphoma, Burkitt lymphoma, and nasopharyngeal carcinoma. -Some infections directly or indirectly weaken the immune system, reducing its ability to detect and eliminate emerging cancer cells.
1170-	INF-γ	↓	interferon gamma			IFN-γ is a cytokine produced primarily by activated T lymphocytes (CD4⁺ Th1, CD8⁺ cytotoxic T cells) and natural killer (NK) cells. – It plays a central role in orchestrating immune responses against pathogens and tumor cells by enhancing antigen presentation and activating immune effector mechanisms. – IFN-γ can promote antitumor immunity by activating macrophages, NK cells, and cytotoxic T lymphocytes. – It enhances the presentation of tumor antigens, thereby facilitating the immune system’s ability to target and eliminate cancer cells. • Its expression and signaling within the tumor microenvironment are generally associated with a robust immune response and, in many cases, a favorable prognosis—particularly in tumors deemed "immunologically hot." • Dual Role: – While IFN-γ typically supports immune-mediated tumor suppression, chronic exposure to IFN-γ within the tumor microenvironment may contribute to immune editing and the selection of tumor cell variants that are resistant to immune attack.
953-	Inflam	↑	inflammation			Cancer and inflammation are closely linked, with chronic inflammation contributing to the development and progression of cancer. Various inflammatory mediators and cells are involved in this process.
159-	iNOS	↑	Inducible nitric oxide synthase	HalifaxProj(block)		an enzyme that produces nitric oxide (NO) in response to inflammatory stimuli. iNOS can promote tumor growth by enhancing blood flow and nutrient supply to tumors through vasodilation. It may also help cancer cells evade apoptosis (programmed cell death). Immune Activation: In some contexts, NO produced by iNOS can enhance the immune response against tumors, promoting the activation of immune cells that can target and destroy cancer cells. Inhibition of Tumor Growth: High levels of NO can induce cytotoxic effects on tumor cells, leading to reduced proliferation and increased apoptosis.
1190-	Insulin	↑	Insulin			Insulin, traditionally known for its role in regulating blood glucose levels, also exerts potent mitogenic (cell division–promoting) effects. Insulin exerts its effects primarily through binding to the insulin receptor (IR), a receptor tyrosine kinase. Upon binding, the receptor undergoes autophosphorylation and activates several downstream signaling cascades, including: -PI3K/Akt Pathway: Overactivation of this pathway is often observed in cancers. -RAS/MAPK Pathway: aberrant activation can lead to tumorigenesis. IR-A: Often predominates in fetal tissues and some cancer cells. It has a higher affinity for insulin-like growth factors (IGFs) and is more mitogenic. IR-B: More involved in metabolic regulation. Studies have shown that many cancers (such as breast, colon, and lung cancers) preferentially overexpress the IR-A isoform
534-	IP-10/CXCL-10	⇅	Interferon-γ(IFN)-inducible protein 10			Interferon-γ-inducible protein 10 (IP-10), also known as CXCL10, is a chemokine that plays a significant role in immune responses, particularly in the recruitment of immune cells to sites of inflammation and infection. Its expression has been studied in various cancers, and it has implications for tumor behavior and the immune response. Interferon-γ-inducible protein 10 is a potent chemoattractant for natural killer cells and activated T lymphocytes. It also displays angiostatic properties and some antitumor activity. IP-10 upregulation correlated with shorter survival provides evidence that IP-10 plays a functional role in pancreatic cancer. Interferon-γ-inducible protein 10 (IP-10) is a potent inhibitor of tumor angiogenesis. It has been reported that the antiangiogenic therapy combined with chemotherapy has synergistic effects. Mixed Prognosis: The prognostic implications of IP-10 in cancer can vary. In some cases, high levels of IP-10 may correlate with a favorable immune response and better prognosis, while in other contexts, it may be associated with tumor progression and poor outcomes.
349-	IR	↑	Insulin Receptor pathway			The Insulin/IR pathway is a major regulator of liver cells growth. The pathway begins when insulin binds to the insulin receptor (IR), a transmembrane receptor that is part of the receptor tyrosine kinase family. The insulin receptor pathway is a critical signaling pathway that regulates various cellular processes, including glucose metabolism, cell growth, and differentiation. Negative Prognosis: In many cancers, overactivation of the insulin receptor pathway is associated with increased tumor aggressiveness, proliferation, and poorer overall survival. High levels of insulin or insulin receptor expression can correlate with worse clinical outcomes.
1051-	IRAK4	↑	interleukin-1 receptor-associated kinase 4			IRAK4 (interleukin-1 receptor-associated kinase 4) is a serine/threonine kinase that plays a crucial role in mediating signaling downstream of toll-like receptors (TLRs) and interleukin-1 receptors (IL-1Rs). Given its involvement in innate immune signaling and the inflammatory response, aberrations in IRAK4 expression or activity can influence oncogenic processes. In hematological malignancies, particularly lymphomas and certain leukemias, increased IRAK4 expression and activity have been observed and are linked to sustained inflammatory signaling, contributing to aggressive disease features and poorer outcomes. • In solid tumors, while data remain more heterogeneous, elevated IRAK4 levels in some cancers correlate with increased inflammation, tumor progression, and resistance to therapy.
618-	IRE1	↑	Inositol-Requiring Enzyme 1			a protein that plays a crucial role in the unfolded protein response (UPR), a cellular stress response mechanism that helps maintain endoplasmic reticulum (ER) homeostasis. IRE1 is activated in response to ER stress, which occurs when the ER is overwhelmed with misfolded or unfolded proteins. IRE1 is overexpressed in various types of cancer, including breast, lung, colon, and pancreatic cancer. This overexpression is often associated with poor prognosis and reduced overall survival.
660-	IRF3	↓	Interferon Regulatory Factor 3			Interferon Regulatory Factor 3 (IRF3) is a transcription factor that plays a crucial role in the regulation of immune responses, particularly in the context of viral infections and cancer. IRF3 is a key component of the innate immune system, which is the first line of defense against pathogens. IRF3 has been shown to have both tumor-suppressive and tumor-promoting functions, depending on the type of cancer and the specific cellular context. Generally, there is lower expression of IRF3 in cancer and is associated with worse prognosis in many cancers, indicating its potential role as a tumor suppressor.
160-	Iron	↑	Iron			Iron is an essential nutrient that is crucial for various cellular processes, including DNA synthesis, cell proliferation, and oxygen transport. Cancer cells often have increased iron requirements due to their rapid growth and proliferation. Some tumors can acquire iron through various mechanisms, including upregulating iron transport proteins. This can support their growth and survival. Excess iron can lead to the production of reactive oxygen species (ROS) through Fenton reactions, which can cause oxidative damage to DNA, proteins, and lipids. This oxidative stress can contribute to cancer development and progression.
835-	IronCh	?	Iron Chelator
464-	IRP1	↑	Iron regulatory protein 1			IRP1, a well-known iron regulatory protein, an important element in the regulation of iron homeostasis in animal cells. glioma patients with high expression of IRP1 had better survival prognosis. Protumorigenic Effects Iron Homeostasis: IRP1 regulates iron metabolism, and its upregulation can lead to increased iron availability, which supports tumor growth and proliferation. Oxidative Stress: Elevated iron levels can contribute to oxidative stress, promoting DNA damage and tumor progression. Cellular Proliferation: By enhancing iron uptake, IRP1 can support the metabolic demands of rapidly dividing cancer cells. Generally, IRP1 has higher expression in cancers and is associated with worse prognosis, indicating its potential role in promoting tumors.
692-	ITGA1	↑	Integrin Subunit Alpha 1		gene	The ITGA1 gene, also known as Integrin Subunit Alpha 1, is a protein-coding gene that plays a crucial role in cell adhesion, migration, and signaling. Integrins are a family of transmembrane receptors that facilitate cell-cell and cell-extracellular matrix interactions. Overexpressed in: Breast, lung, CRC prostate
548-	ITGA11	↑	Integrin α11			a crucial cell adhesion receptor involved in diverse biological processes. ITGA11 expression is associated with poor prognoses. It significantly influences the tumor microenvironment by regulating collagen assembly and matrix remodeling, particularly through pathways such as TGF-β and Hedgehog signaling. Moreover, ITGA11 contributes to cancer progression via interconnected pathways like PI3K/AKT and PDGFBR/JNK, influencing tumor growth, invasion, and metastasis. ITGA11 is also highly expressed in fibroblasts of head and neck, breast, pancreas, lung, colorectal and Gastric Cancer .
863-	ITGA5	↑	Integrin alpha 5			ITGA5 (Integrin alpha 5) is a protein that plays a crucial role in cell adhesion, migration, and signaling. It is a transmembrane receptor that interacts with various extracellular matrix proteins, such as fibronectin, to regulate cell behavior. ITGA5 has been shown to promote tumor growth, invasion, and metastasis by facilitating cell adhesion, migration, and angiogenesis. ITGA5 is a gene that encodes for the alpha 5 subunit of the integrin alpha 5 beta 1 (α5β1) receptor. Integrins are a family of transmembrane receptors that play a crucial role in cell adhesion, migration, and signaling. ITGA5 has been found to be overexpressed in various types of tumorsand its expression has been associated with poor prognosis.
669-	ITGB1	↑	Integrin beta-1			ITGB1, also known as Integrin beta-1, is a protein that plays a crucial role in cell adhesion, migration, and signaling. It is a transmembrane receptor that interacts with various extracellular matrix proteins, such as collagen, laminin, and fibronectin. ITGB1 is overexpressed in: breast, lung, colon, prostate, CRC, ovarian, pancreatic, gastric, esophageal, melanoma, GBM
231-	ITGB4	↑	Integrin Subunit Beta 4		gene	The ITGB4 gene, also known as Integrin Subunit Beta 4, plays a crucial role in cell adhesion and signaling. It is a member of the integrin family, which are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix interactions. ITGB4 contributes to cancer development and progression
233-	ITGB6	↑	Integrin Subunit Beta 6			The ITGB6 gene, also known as Integrin Subunit Beta 6, is a protein-coding gene that plays a crucial role in cell adhesion and signaling. ITGB6 is a member of the integrin family, which are transmembrane receptors that facilitate cell-cell and cell-extracellular matrix interactions. ITGB6 is specifically expressed in epithelial cells and is involved in the regulation of cell adhesion, migration, and proliferation. Overexpressed in: Esophageal, Gastric, Breast, lung
161-	IκB	↓	IκB kinase(α)			IκB (Inhibitor of Nuclear Factor kappa B) proteins are critical regulators of the NF-κB signaling pathway, which plays a significant role in inflammation, immune response, and cell survival. IκB kinase/NF-κB (IKK/NF-κB) signaling pathways play critical roles in a variety of physiological and pathological processes. One function of NF-κB is promotion of cell survival through induction of target genes, whose products inhibit components of the apoptotic machinery in normal and cancerous cells. NFKB inhibitor α (IκB‑α) acts as a negative regulator of the classical NF‑κB pathway through its ability to maintain the presence of NF‑κB in the cytoplasm. IκB (Inhibitor of κB) proteins play a crucial role in regulating the NF-κB (Nuclear Factor kappa-light-chain-enhancer of activated B cells) signaling pathway, which is involved in various cellular processes, including inflammation, immune response, and cell survival. The NF-κB pathway is tightly regulated, and its dysregulation has been implicated in the development and progression of various cancers. In many cancers, the degradation of IκB is enhanced, leading to constitutive activation of NF-κB. This can promote tumor growth and survival by upregulating genes involved in cell proliferation and anti-apoptotic factors. IκB proteins generally act as tumor suppressors by inhibiting NF-κB activity. When IκB is downregulated, NF-κB is activated, leading to increased cell proliferation, survival, and inflammation, which can promote tumor growth. It is generally down regulated in cancers, with poorer prognosis.
162-	JAK	↑	Janus kinases	HalifaxProj(inhibit)		a family of enzymes that play a crucial role in the signaling pathways of various cytokines and growth factors. They are involved in the regulation of immune responses, hematopoiesis, and cell proliferation. Dysregulation of JAK signaling has been implicated in several types of cancer, particularly hematological malignancies such as leukemia and lymphoma. Targeting JAKs with specific inhibitors has emerged as a therapeutic strategy in oncology. JAK inhibitors, such as ruxolitinib and tofacitinib, are used to treat certain blood cancers and autoimmune diseases. These drugs work by blocking the activity of JAKs, thereby inhibiting the signaling pathways that promote cancer cell proliferation and survival.
163-	JAK1	↑	Janus kinase 1	CGL-Driver Genes	Oncogene	one of the four members of the Janus kinase family and plays a significant role in the signaling pathways of various cytokines and growth factors, particularly those involved in immune responses. Its involvement in cancer has been increasingly recognized, as dysregulation of JAK1 signaling can contribute to tumorigenesis and cancer progression. JAK1 is primarily associated with the signaling of several key cytokines, including interleukins (e.g., IL-2, IL-6, IL-10) and interferons. These cytokines are crucial for immune responses, and their dysregulation can lead to inhibitors, such as those targeting JAK1 specifically, are being investigated in clinical trials for various malignancies, including solid tumors and hematological cancers. an environment that supports cancer growth.
164-	JAK2	↑	Janus kinase 2	CGL-Driver Genes	Oncogene	a tyrosine kinase that plays a crucial role in the signaling pathways of various cytokines and growth factors. It is particularly important in hematopoiesis (the formation of blood cells) and immune responses. JAK2 plays a significant role in cancer biology, particularly in hematological malignancies, where its expression and activity are often upregulated. Increased JAK2 activity is generally associated with worse prognosis in many cancers, indicating its potential role in promoting tumor growth and survival
165-	JAK3	↑	Janus kinase 3	CGL-Driver Genes	Oncogene	a member of the Janus kinase family of enzymes, which play a crucial role in the signaling pathways of various cytokines and growth factors. JAK3 is primarily expressed in hematopoietic (blood-forming) cells and is involved in the signaling of several interleukins, particularly those that are important for immune function. mutations in the JAK3 gene can lead to constitutive activation of the pathway, promoting uncontrolled cell proliferation and survival.
167-	JAML	⇅	Junctional Adhesion Molecule-Like			major co-stimulatory molecule in epithelial γδ T cells a protein that plays a role in cell adhesion and is involved in various biological processes, including immune responses and inflammation. JAML can influence tumor progression and metastasis by affecting the behavior of immune cells and the tumor microenvironment. JAML is expressed on certain immune cells, such as T cells and dendritic cells. Its role in immune cell adhesion and migration may affect the infiltration of immune cells into tumors, potentially impacting the effectiveness of anti-tumor immune responses. Higher or lower levels of JAML expression may correlate with patient outcomes, although findings can vary depending on the type of cancer. Tumor Suppressive Role: In some contexts, JAML may act as a tumor suppressor by promoting cell adhesion and immune cell interactions, which can enhance anti-tumor immunity. Tumor Promoting Role: Conversely, in certain tumor microenvironments, JAML may facilitate tumor progression by promoting cell adhesion and migration, potentially aiding in metastasis. In BC, CRC, and lung cancers low levels generally mean worse prognosis.
168-	JNK	↑	c-Jun N-terminal kinase (JNK)			JNK acts synergistically with NF-κB, JAK/STAT, and other signaling molecules to exert a survival function. Janus signaling promotes cancer cell survival. JNK, or c-Jun N-terminal kinase, is a member of the mitogen-activated protein kinase (MAPK) family. It plays a crucial role in various cellular processes, including cell proliferation, differentiation, and apoptosis (programmed cell death). JNK is activated in response to various stress signals, such as UV radiation, oxidative stress, and inflammatory cytokines. JNK activation can promote apoptosis in cancer cells, acting as a tumor suppressor. However, in other contexts, it can promote cell survival and proliferation, contributing to tumor progression. JNK is often unregulated in cancers, leading to increased cancer cell proliferation, survival, and resistance to apoptosis. This activation is typically associated with poor prognosis and aggressive tumor behavior.
169-	Jun	↑	Jun			The JUN proto-oncogene is a gene that encodes a protein called c-Jun, which is a component of the AP-1 (Activator Protein 1) transcription factor complex. Jun is a key component of the AP-1 (Activator Protein 1) transcription factor complex, which plays a significant role in regulating gene expression in response to various stimuli, including growth factors, stress, and cytokines. The Jun family includes several proteins, such as c-Jun, JunB, and JunD, which can have distinct roles in cancer biology. In many cancers, Jun, particularly c-Jun, is activated and promotes cell proliferation, survival, and invasion. This activation is typically associated with poor prognosis and aggressive tumor behavior.
845-	JWA	↓	JWA protein or JWA gene			JWA (also known as JWA protein or JWA gene) is a protein that has been implicated in various cellular processes, including cell cycle regulation, apoptosis, and DNA repair. JWA is frequently downregulated or mutated in various types of cancer, including breast, lung, colon, and ovarian cancer. JWA, a microtubular binding tumour suppressor protein that downregulates topoisomerase II-alpha, resulting in G2/M arrest in NSCLC cells
1211-	K17	↑	Keratin 17			Keratin 17 (K17) is an intermediate filament protein that has emerged as more than just a structural component in epithelial cells -K17 is frequently upregulated in certain subtypes of breast, CC, SCC cancer, especially in triple-negative breast cancers (TNBC). –Prognosis: High K17 expression has been correlated with aggressive tumor behavior, higher proliferation rates, and poorer overall survival. It is emerging as a marker for tumor aggressiveness in this context.
702-	KCNQ1OT1	↑	KCNQ1OT1		long non-coding RNA (lncRNA)	KCNQ1OT1 is a long non-coding RNA (lncRNA) that has been implicated in various types of cancer. It is located on chromosome 11p15.5, a region that is often associated with cancer and other diseases. KCNQ1OT1 is overexpressed in several types of cancer, including: HCC, Colorectal cancer, Breast, Lung, Ovarian.
170-	KDM5C	↓	lysine (K)-specific demethylase 5C	CGL-Driver Genes	TSG	KDM5C (Lysine Demethylase 5C) is a member of the KDM5 family of histone demethylases, which are enzymes that play a crucial role in the regulation of gene expression by removing methyl groups from lysine residues on histone proteins. KDM5C has been suggested to function as a tumor suppressor in certain types of cancer. Its loss or downregulation can lead to increased cell proliferation and tumorigenesis. For example, studies have shown that KDM5C can inhibit the expression of oncogenes and promote the expression of tumor suppressor genes. Inhibitors of KDM5C or modulators of its activity may offer new avenues for cancer treatment, particularly in cancers where KDM5C is found to be dysregulated. In many cancers, KDM5C is down regulated, acts as a tumor suppressor, where its downregulation is associated with increased tumor growth, invasion, and poor prognosis. This is often due to its role in regulating gene expression related to cell cycle control and apoptosis.
171-	KDM6A	↓	lysine (K)-specific demethylase 6A	CGL-Driver Genes	TSG	KDM6A (Lysine Demethylase 6A) is a gene that encodes a protein involved in the regulation of gene expression through the demethylation of histone proteins. It plays a crucial role in epigenetic regulation, which is the process by which gene activity is regulated without changes to the underlying DNA sequence. KDM6A is often considered a tumor suppressor gene. Loss of function mutations or deletions of KDM6A have been observed in several cancers, including bladder cancer, lung cancer, and certain hematological malignancies. In many cancers, KDM6A is often downregulated or mutated, leading to a loss of its demethylase activity. This downregulation can result in the accumulation of repressive histone marks, such as H3K27me3, which can silence tumor suppressor genes and promote oncogenic pathways.
789-	KDR/FLK-1	↑	Kinase insert Domain-Containing Receptor/Fetal Liver Kinase-1		receptor tyrosine kinase	KDR/FLK-1 (Kinase insert Domain-Containing Receptor/Fetal Liver Kinase-1) is a receptor tyrosine kinase that plays a crucial role in angiogenesis, the process of new blood vessel formation.
1174-	Keap1	↓	Kelch-like ECH-associated protein 1			Kelch-like ECH-associated protein 1 (Keap1) is a key regulator of the transcription factor Nrf2. -In several tumor types, loss of Keap1 function (either due to gene mutations or low protein expression) results in unrestrained Nrf2 activity. • Persistent Nrf2 activation is thought to:  - Provide tumor cells with enhanced protection against oxidative stress.  - Contribute to chemoresistance and radioresistance.  - Promote metabolic reprogramming that fuels tumor growth. • Thus, in many cancers, altered Keap1 status can serve as an indicator of poor prognosis and has been investigated as a potential target for therapeutic intervention.
1187-	KeyT	∅	Keytones			A ketogenic diet is high in fats and low in carbohydrates, which shifts the body’s metabolism to produce ketone bodies (such as β-hydroxybutyrate and acetoacetate) as an alternative energy source. The three main ketone bodies are: -Beta-hydroxybutyrate (BHB): The most abundant and commonly measured ketone in the blood. -Acetoacetate: Can be measured in both the blood and urine. -Acetone: Often measured in the breath; it is a byproduct of acetoacetate breakdown. 1. Blood Ketone Meters (accurate, fast) -Nutritional ketosis is often defined by BHB levels between 0.5 to 3.0 mmol/L. 2. Urine Ketone Strips (urine test may not accurately reflect blood levels) 3. Breath Ketone Analyzers(not always perfectly correlate with blood BHB concentrations.)
425-	Ki-67	↑	Ki-67 protein		proliferation marker	A high Ki-67 proliferation index means many cells are dividing quickly and that the cancer is likely to grow and spread. markers of proliferation index (Ki-67) • Ki-67 serves primarily as a proliferation marker: higher levels are generally indicative of aggressive disease and poorer outcomes across many cancer types. • While Ki-67 itself is not considered a driver of tumorigenesis, its expression mirrors the high proliferative activity associated with protumoral behavior. • It is widely used in clinical practice to aid in tumor grading, prognostication, and treatment planning.
1304-	KIF2C	↑	Kinesin Family Member 2C			KIF2C (Kinesin Family Member 2C), also known as Mitotic Centromere-Associated Kinesin (MCAK), is a microtubule-depolymerizing motor protein that plays an essential role in chromosome segregation during mitosis • Numerous studies have documented that KIF2C is frequently overexpressed in various tumor types, including breast, lung, colorectal, and hepatocellular carcinomas. • Elevated expression levels are often observed in aggressive or advanced stages of cancers, reflecting its role in supporting the rapid proliferation of malignant cells.
1186-	KISS1	↓	KISS1			Kiss1 is widely recognized as a metastasis suppressor in several cancers Kiss1 serves as an important metastasis suppressor gene whose expression is generally linked to a less aggressive clinical course in cancers such as breast cancer and melanoma
172-	KIT	↑		CGL-Driver Genes	Oncogene	similar to Mast/stem cell growth factor receptor precursor (SCFR) (Proto-oncogene tyrosine-protein kinase Kit) (c-kit) (CD117 antigen); v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog KIT protein is also known as the stem cell factor receptor (SCFR) or CD117. It is a type of receptor tyrosine kinase that binds to its ligand, stem cell factor (SCF). This interaction is crucial for various biological processes, including hematopoiesis (the formation of blood cells), melanogenesis (the formation of melanin in skin cells), and the development of certain types of immune cells. In some cases, high KIT expression may be associated with a poorer prognosis. Targeted therapies that inhibit KIT signaling are being explored in clinical settings for cancers where KIT plays a role.
1196-	KLF2	↓	Krüppel-like factor 2			KLF2 is a zinc finger transcription factor that contributes to the regulation of cell differentiation, proliferation, apoptosis, and inflammation. – In breast cancer(and CRC), several studies have reported that KLF2 expression is decreased in more aggressive tumor subtypes. – Reduced KLF2 levels are often associated with enhanced cell proliferation, migration, and invasion, which may contribute to a worse prognosis.
173-	KLF4	↓	Kruppel-like factor 4	CGL-Driver Genes	Oncogene	KLF4 (Kruppel-like factor 4) is a transcription factor that plays a significant role in various biological processes, including cell differentiation, proliferation, and apoptosis. KLF4 has a complex role in cancer, acting as both a tumor suppressor and an oncogene depending on the specific cancer type and context. In many cancers, KLF4 acts as a tumor suppressor, where its downregulation is associated with increased tumor growth, invasion, and poor prognosis. This is often due to its role in regulating genes involved in cell cycle control, differentiation, and apoptosis. KLF4 levels, which plays an important role in stem cell formation.
1195-	KLF5	↑	Krüppel-like factor 5			KLF5 is a zinc finger transcription factor that plays crucial roles in regulating cell proliferation, differentiation, survival, migration, and angiogenesis. – KLF5 is often overexpressed in certain subtypes and has been implicated in promoting cell proliferation and survival. – Evidence suggests that high KLF5 levels can be associated with increased tumor aggressiveness and may contribute to resistance to therapy in some contexts.
174-	KRAS	↑	v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog	CGL-Driver Genes	Oncogene	KRAS (Kirsten rat sarcoma viral oncogene homolog) is a gene that encodes a protein involved in cell signaling pathways that control cell growth and division. Mutations in the KRAS gene are among the most common genetic alterations found in various types of cancer, particularly pancreatic, colorectal, and lung cancers. Mutations in the KRAS gene lead to the production of a hyperactive KRAS protein. Cancers with KRAS mutations are often more aggressive and associated with poorer prognosis.
974-	L-sel	↓	L‑selectin/CD62L			also known as CD62L CD62L is a cell adhesion molecule expressed mainly on leukocytes (e.g., naïve and central memory T cells, B cells, and some neutrophils). • It mediates lymphocyte homing to lymph nodes and can be involved in leukocyte recruitment to inflammatory sites. • CD62L can be shed from the cell surface, leading to a soluble form detectable in plasma. In some cancer settings, elevated soluble CD62L has been associated with tumor progression. Lower expression usually associated with poorer outcomes
950-	lact/pyru	↑	lactate/pyruvate ratio			The lactate/pyruvate ratio is a measure of the balance between lactate and pyruvate, two key metabolites involved in cellular energy metabolism. In cancer, the lactate/pyruvate ratio is often increased, which is often associated with poor prognosis.
739-	lactateProd	↑	lactate production			Lactate production has been linked to cancer development and progression. In normal conditions, lactate is produced in cells through a process called glycolysis, which breaks down glucose to generate energy. However, in cancer cells, this process is often upregulated, leading to increased lactate production, even in the presence of oxygen. This phenomenon is known as the Warburg effect. -Lactate is the end product of glycolysis and induces TGFβ1 upregulation and the acidic microenvironment
423-	LAMA5	↑	laminin alpha 5		gene	The LAMA5 gene is a gene that encodes for the laminin alpha 5 chain, a protein that is part of the laminin family. Laminins are high-molecular weight glycoproteins that are a major component of the basement membrane, a layer of tissue that separates epithelial cells from the underlying connective tissue. Overexpressed in: Breast, lung, CRC, Prostate
545-	LAMB3	↑	Laminin subunit beta-3			a protein that in humans is encoded by the LAMB3 gene. LAMB3 is highly expressed in numerous tumorous and non-tumorous conditions, including renal fibrosis; squamous cell carcinoma of the skin, thyroid, lung, pancreatic, ovarian, colorectalr, gastric, breast, cervical, nasopharyngeal, bladder, prostate cancers; and cholangiocarcinoma. Conversely, it is underexpressed in other conditions, such as hepatocellular carcinoma, epidermolysis bullosa, and amelogenesis imperfecta.
1101-	LAMP1	↑	Lysosome-Associated Membrane Protein 1			LAMP1 is a major glycoprotein of the lysosomal membrane and plays key roles in lysosome stability, cellular homeostasis, and autophagy. • Beyond its lysosomal function, LAMP1 is implicated in cell adhesion, migration, and invasion processes. Elevated LAMP1 expression is frequently linked to advancements in tumor aggressiveness, metastasis, and poorer clinical outcomes in several cancer types.
855-	LAMP2	↑	Lysosome-Associated Membrane Protein 2			LAMP-2 (Lysosome-Associated Membrane Protein 2) is a protein that plays a crucial role in the function and maintenance of lysosomes, which are organelles responsible for cellular digestion and recycling. LAMP-2 is involved in the regulation of autophagy, a process by which cells recycle damaged or dysfunctional components. Cancer cells often exploit autophagy to promote their survival and growth. LAMP-2 is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. High LAMP-2 expression is correlated with poor prognosis, including reduced overall survival and increased risk of recurrence.
740-	LAR	↑	lactate receptor			lactate receptor is GPR81, but it is also commonly referred to as HCAR1 (Hydroxycarboxylic Acid Receptor 1) or LAR (Lactate Receptor), due to its ability to bind lactate. -is a G protein-coupled receptor that plays a crucial role in various physiological processes, including glucose and lipid metabolism, and inflammation. HCAR-1 is overexpressed in various types of cancer, including breast, lung, colon, and pancreatic cancer. This overexpression is often associated with poor prognosis and reduced survival rates.
345-	LAT	↑	L-Type Amino Acid Transporter			L-Type Amino Acid Transporter 1 (LAT1) mediates the uptake of essential amino acids and its expression is upregulated during the progression of several cancers. By upregulating amino acid transporters, cancer cells gain greater access to exogenous amino acids to support chronic proliferation, maintain metabolic pathways, and to enhance certain signal transduction pathways. In many cancers it is unregulated, particularly those with high metabolic demands, LATs, especially LAT1, facilitate the uptake of essential amino acids that support protein synthesis, cell growth, and proliferation. This is typically associated with poor prognosis and aggressive tumor behavior.
346-	LATgene	↓	linker for activation of T cells			LAT gene (linker for activation of T cells). As an adaptor protein, the function of LAT in TCR signaling centers upon its tyrosine phosphorylation and subsequent recruitment of other signaling proteins. LAT (Linker for Activation of T cells) plays a significant role in T cell signaling and immune responses, with its expression levels and functional outcomes varying across different cancer types. Generally, decreased LAT expression is associated with worse prognosis in many cancers, indicating its potential role as a tumor suppressor through the enhancement of anti-tumor immunity.
685-	LC3‑Ⅱ/LC3‑Ⅰ	↑	ratio of LC3‑Ⅱ/LC3‑Ⅰ		marker	The ratio of LC3-II to LC3-I is often used as a marker for autophagy, a cellular process in which cells recycle their damaged or dysfunctional components. In cancer, autophagy can play a complex role, and the LC3-II/LC3-I ratio can be used to assess autophagic activity. Many cancers, have an increased LC3-II/LC3-I ratio indicating enhanced autophagy, which can support tumor cell survival, especially under stress conditions (e.g., nutrient deprivation, hypoxia). This is often associated with poor prognosis and treatment resistance. Cell Survival: Increased autophagy, as indicated by a higher LC3-II/LC3-I ratio, can help cancer cells survive in adverse conditions, contributing to tumor growth and metastasis. Therapeutic Resistance: Elevated autophagy can lead to resistance against chemotherapy and targeted therapies, as cancer cells may utilize autophagy to survive treatment-induced stress. Metabolic Adaptation: Autophagy allows cancer cells to adapt to metabolic stress by recycling cellular components, which can support continued proliferation and survival.
1282-	LC3A	↑	Microtubule-associated protein 1 light chain 3 alpha			LC3A is one of the isoforms of the LC3 family and plays a critical role in the autophagy pathway. – Enhanced Autophagy and Tumor Survival: In some cancers, increased LC3A expression (and therefore autophagic activity) is associated with a cytoprotective response, helping tumor cells survive under stress conditions such as hypoxia, nutrient deprivation, or treatment-induced damage. This has been linked in some cases to more aggressive tumor behavior and resistance to therapies.
1081-	LC3B	↑	microtubule-associated protein 1 light chain 3 beta			LC3B (microtubule-associated protein 1 light chain 3 beta) is a key protein involved in the autophagy pathway and is widely used as a marker to assess autophagic activity in cells. While not a classical immunogenic cell death (ICD) marker, its expression in tumors has been linked with several prognostic implications, often reflecting the balance between autophagy’s tumor-suppressive and tumor-promoting roles. • LC3B plays a central role in autophagosome formation. • Its conversion from LC3BI (cytosolic form) to LC3BII (lipidated, membrane-bound form) is a key indicator of autophagy activation. • LC3B is sometimes evaluated together with other autophagy-related proteins (such as Beclin-1) to generate an overall picture of autophagic activity in the tumor. – In several cancers (e.g., pancreatic, colorectal, and breast cancers), elevated LC3B levels have been associated with enhanced autophagy, which can promote tumor cell survival under stress conditions (such as hypoxia or chemotherapy). – Certain studies, particularly in early-stage tumors or specific subtypes, have found that higher LC3B correlates with improved outcomes.
1208-	LC3B-II	↑	LC3B-II			LC3B-II is a lipidated form of LC3B that is widely used as a marker for autophagy. -Several studies have reported that higher levels of LC3B-II correlate with more aggressive tumor behavior. -Prognostic Implication: Increased LC3B-II expression is often associated with poorer prognosis, including reduced overall survival and disease‐free survival. This may reflect a role for autophagy in tumor cell survival under stress. -Dual Role of Autophagy: Autophagy (and therefore LC3B-II expression) may act as both a tumor suppressor and a tumor promoter depending on the tumor type, stage, and microenvironment.
720-	LC3I	↓	Lysosomal-associated membrane protein 2A			LC3I (Lysosomal-associated membrane protein 2A, also known as LAMP2A) is a protein that plays a crucial role in the process of chaperone-mediated autophagy (CMA). CMA is a type of autophagy, a cellular process in which cells recycle and remove damaged or dysfunctional components. LC3I is overexpressed in certain types of cancer, including breast, lung, and colon cancer. The conversion of LC3-I to LC3-II (the lipidated form) is a key step in autophagy activation. : In many cancers, low levels of LC3-I may indicate impaired autophagy, which can lead to the accumulation of damaged proteins and organelles, contributing to tumorigenesis. This is often associated with poor prognosis. Tumor Promoting Role: In some contexts, the presence of LC3-I may indicate a baseline level of autophagy that is necessary for cellular homeostasis, but its role is less prominent compared to LC3-II. Generally, decreased expression of LC3-I is associated with worse prognosis in many cancers, indicating its potential role in tumor suppression through the regulation of autophagy. However, the context-dependent nature of LC3-I's function suggests that further research is needed to fully understand its roles in different cancer types and its potential as a therapeutic target.
721-	LC3II	↑	Microtubule-associated protein 1A/1B light chain 3			LC3II (Microtubule-associated protein 1A/1B light chain 3, also known as LC3) is a protein that plays a crucial role in the process of autophagy. Autophagy is a cellular process in which cells recycle and remove damaged or dysfunctional components. LC3II is often used as a marker for autophagy, as its levels increase during autophagic activity. LC3II is overexpressed in certain types of cancer, including breast, lung, and colon cancer. LC3II is also known by other names, including: MAP1LC3B (Microtubule-associated protein 1 light chain 3 beta) LC3B (Microtubule-associated protein 1 light chain 3 beta) ATG8F (Autophagy-related protein 8F) : In many cancers, increased LC3-II expression indicates enhanced autophagy, which can support tumor cell survival, especially under stress conditions (e.g., nutrient deprivation, hypoxia). This is often associated with poor prognosis and treatment resistance.
492-	LC3s	↑	Autophagosome Proteins			LC3s (MAP1-LC3A, B and C) are structural proteins of autophagosomal membranes, widely used as biomarkers of autophagy. Whether these three LC3 proteins have a similar biological role in autophagy remains obscure. Protumorigenic: In many cases, especially in advanced cancers, increased autophagy (reflected by high LC3 levels) can support tumor growth by providing nutrients and promoting cell survival under stress conditions. Antitumorigenic: Conversely, in early-stage tumors or in response to certain therapies, autophagy can act as a tumor suppressor by preventing the accumulation of damaged organelles and proteins.
906-	LDH	↑	Lactate Dehydrogenase			LDH is a general term that refers to the enzyme that catalyzes the interconversion of lactate and pyruvate. LDH is a tetrameric enzyme, meaning it is composed of four subunits. LDH refers to the enzyme as a whole, while LDHA specifically refers to the M subunit. Elevated LDHA levels are often associated with poor prognosis and aggressive tumor behavior, similar to elevated LDH levels. However, it's worth noting that some studies have shown that LDHA is a more specific and sensitive biomarker for cancer than total LDH, as it is more closely associated with the Warburg effect and cancer metabolism. Dysregulated LDH activity contributes significantly to cancer development, promoting the Warburg effect (Chen et al., 2007), which involves increased glucose uptake and lactate production, even in the presence of oxygen, to meet the energy demands of rapidly proliferating cancer cells (Warburg and Minami, 1923; Dai et al., 2016b). LDHA overexpression favors pyruvate to lactate conversion, leading to tumor microenvironment acidification and aiding cancer progression and metastasis Inhibitors: https://pmc.ncbi.nlm.nih.gov/articles/PMC10616500/ Flavonoids, a group of polyphenols abundant in fruit, vegetables, and medicinal plants, function as LDH inhibitors • Galloflavin: A flavonoid compound found in the plant Galphimia gracilis, which has been shown to inhibit LDH and have anti-cancer activity. • Fisetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Quercetin: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Kaempferol: A flavonoid compound found in various fruits and vegetables, which has been shown to inhibit LDH and have anti-cancer activity. • Resveratrol: A polyphenol compound found in grapes and other plants, which has been shown to inhibit LDH and have anti-cancer activity. • Curcumin: A polyphenol compound found in turmeric, which has been shown to inhibit LDH and have anti-cancer activity. • Berberine: A compound found in the plant Berberis, which has been shown to inhibit LDH and have anti-cancer activity. • Honokiol: A lignan compound found in the plant Magnolia, which has been shown to inhibit LDH and have anti-cancer activity. • Silibinin: A flavonoid compound found in milk thistle, which has been shown to inhibit LDH and have anti-cancer activity. Others:Ursolic acid, Oleanolic acid, Limonin, Allicin (garlic), Taurine
175-	LDHA	↑	Lactate dehydrogenase A			LDHA is a key enzyme that catalyzes the conversion of pyruvate into lactate while regenerating NAD+, essential for glycolysis Elevated levels of LDHA have been associated with increased tumor growth and survival. By promoting lactate production, cancer cells can create an acidic microenvironment that may facilitate invasion and metastasis. is often upregulated in various types of cancer, including breast, lung, colorectal, and prostate cancers. This upregulation is associated with the metabolic shift that cancer cells undergo to support rapid growth and proliferation. Measuring the lactate dehydrogenase (LDH) is a useful method for detection of necrosis.
925-	LDHB	↑	Lactate dehydrogenase B			Lactate dehydrogenase B (LDHB) is an enzyme that plays a crucial role in energy metabolism. Recent studies have shown that LDHB is overexpressed in various types of cancer, and its expression is associated with cancer progression and prognosis.
71-	LDL	↑	LDL-cholesterol			The relationship between LDL (low-density lipoprotein) cholesterol and cancer is a complex and evolving area of research. LDL cholesterol is often referred to as "bad" cholesterol because high levels are associated with an increased risk of cardiovascular diseases. Protumorigenic: High levels of LDL cholesterol can promote tumor growth by providing lipids that are essential for cell membrane synthesis and energy production. Additionally, LDL can influence inflammation and angiogenesis, further supporting tumor development. Antitumorigenic: Some studies suggest that lowering LDL cholesterol through lifestyle changes or medications (like statins) may have a protective effect against certain cancers, although the evidence is not uniform across all cancer types.
384-	LEF1	↑	Lymphoid enhancer-binding factor 1			LEF1 is essential in stem cell maintenance and organ development, especially in its role in epithelial-mesenchymal transition (EMT) by activating the transcription of hallmark EMT effectors including N-Cadherin, Vimentin, and Snail. Aberrant expression of LEF1 is implicated in tumorigenesis and cancer cell proliferation, migration, and invasion. LEF1's activity in particular cancer cell types, such as chronic lymphocytic leukemia (CLL), Burkitt lymphoma (BL), acute lymphoblastic leukemia (ALL), oral squamous cell carcinoma (OSCC), and colorectal cancer (CRC), makes it a valuable biomarker in predicting patient prognosis. https://pubmed.ncbi.nlm.nih.gov/28670499/ LEF1 is often considered protumorigenic due to its role in promoting cell proliferation and survival through the Wnt signaling pathway. Its activation can lead to enhanced tumor growth and metastasis.
831-	Let-7	↓	Let-7		miRNAs	Let-7 is a family of microRNAs (miRNAs) that play a crucial role in regulating gene expression. Let-7 miRNAs are known to target genes involved in cell proliferation, differentiation, and survival, and have been shown to act as tumor suppressors. In cancer, let-7 miRNAs are often downregulated, leading to the upregulation of their target genes, which can contribute to cancer development and progression.
688-	LGR5	↑	Leucine-rich repeat-containing G-protein coupled receptor 5			LGR5 (Leucine-rich repeat-containing G-protein coupled receptor 5) is a protein that plays a crucial role in the development and maintenance of stem cells in various tissues, including the intestine, stomach, and hair follicles. LGR5 is overexpressed in various types of cancer, including colorectal, breast, and ovarian cancer. In these cancers, LGR5 has been found to promote the self-renewal and proliferation of cancer stem cells, leading to tumor growth and metastasis. Inhibiting LGR5 activity has been shown to reduce the growth and self-renewal of cancer stem cells, leading to tumor regression and improved survival in preclinical models.
590-	LIF	↑	leukemia inhibitory factor			(LIF) is a type of protein that plays a crucial role in various cellular processes, including cell growth, differentiation, and survival. It is a member of the interleukin-6 (IL-6) family of cytokines and is involved in the regulation of the immune system, inflammation, and hematopoiesis (the formation of blood cells). LIF has been shown to promote tumor growth and metastasis, and to contribute to the development of cancer stem cells. Inhibiting LIF signaling may provide a novel approach to cancer therapy. (LIF) is expressed in various types of cancer, and its expression has been associated with tumor progression, metastasis, and poor prognosis. (Ovarian, Leukemia, Melanoma, Glioblastoma, Colorectal, Prostrate)
453-	lipid-P	↑	lipid peroxidation			Lipid peroxidation is a chain reaction process in which free radicals (often reactive oxygen species, or ROS) attack lipids containing carbon-carbon double bonds, especially polyunsaturated fatty acids. This attack results in the formation of lipid radicals, peroxides, and subsequent breakdown products. Lipid peroxidation can cause damage to cell membranes, leading to increased permeability and disruption of cellular functions. This damage can initiate a cascade of events that may contribute to carcinogenesis. The byproducts of lipid peroxidation, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), can form adducts with DNA, leading to mutations. These mutations can disrupt normal cellular processes and contribute to the development of cancer. Lipid peroxidation damages cell membranes, disrupts cellular functions, and can trigger inflammatory responses. It is a marker of oxidative stress and is implicated in many chronic diseases. Negative Prognostic Indicator: In many cancers, high levels of lipid phosphates, particularly S1P, are associated with poor prognosis, indicating a more aggressive tumor phenotype and potential resistance to therapy. Mixed Evidence: The prognostic significance of lipid phosphates can vary by cancer type, with some studies showing that their expression may not always correlate with adverse outcomes.
1147-	lipidDe	↑	Lipid Deposition			Lipid deposition refers to the process by which lipids (fats) accumulate in tissues. Key Markers Implicated in Lipid Deposition with Prognostic Relevance Fatty Acid Synthase (FASN):key enzyme in de novo lipogenesis, catalyzing the synthesis of palmitate. -Frequently overexpressed in cancers, associated with aggressive tumor behavior, resistance to therapy, and poorer overall survival. SREBP-1: A transcription factor that upregulates lipogenic genes (including FASN, ACC, and SCD1). -Overactive in various cancers, correlates with enhanced lipogenesis, increased proliferation, and worse prognosis. ACC:Catalyzes the conversion of acetyl-CoA to malonyl-CoA, a crucial step in fatty acid synthesis. -Overactivity may contribute to increased lipid deposition in tumors, promoting growth and associated with poor outcomes. SCD1: Catalyzes the desaturation of saturated fatty acids to monounsaturated fatty acids, important for membrane fluidity and signaling. -Upregulated in cancers, linked to tumor progression, resistance to apoptosis, and a poorer prognosis. CD36: A fatty acid translocase that facilitates the uptake of long-chain fatty acids and is involved in lipid storage. -Overexpression in various cancer, associated with metastatic potential and worse clinical outcomes. FABPs, (FABP4 and FABP5): Intracellular lipid chaperones that help transport fatty acids and other lipids within cells. -Typically Increased expression in cancers, may correlate with increased lipid uptake/storage, contributing to tumor aggressiveness and poorer survival in some cancer types. Lipid Droplet–Associated Proteins (Perilipins PLIN2 and PLIN3) -Involved in the formation and regulation of lipid droplets, which serve as intracellular lipid storage organelles. -Increased lipid droplet accumulation has been linked to chemotherapy resistance and a worse prognosis in certain cancers.
1039-	lipidLev	↑	Lipid Levels			Lipid levels refer to the concentration and distribution of various lipids—including fatty acids, cholesterol, phospholipids, and triglycerides—in cells and tissues. Lipids are essential components of cellular membranes, serve as energy storage molecules, and act as signaling molecules that regulate cellular processes such as growth, apoptosis, and inflammation. Under normal physiological conditions, lipid levels are tightly regulated by dietary intake, de novo synthesis, uptake, storage, and breakdown. Enzymes (e.g., fatty acid synthase, acetyl-CoA carboxylase) and transcription factors (e.g., SREBP1) coordinate these processes to maintain cellular homeostasis. Many tumors upregulate de novo lipogenesis to generate lipids internally, even in the presence of exogenous lipids. As a result, cancer cells often have elevated levels of fatty acids and other lipid intermediates. These adjustments not only support rapid growth but also contribute to resistance to stress and apoptosis.
1038-	lipoGen	↑	lipogenesis			Lipogenesis is the metabolic process by which simple substrates like acetyl-CoA are converted into fatty acids, which are then assembled into complex lipids. This process is essential for producing cell membranes, signaling molecules, and energy storage forms, such as triglycerides. In normal physiology, lipogenesis is tightly regulated by nutritional and hormonal signals to meet the needs of different tissues. key enzymes (e.g. acetyl-CoA carboxylase [ACC], fatty acid synthase [FASN]) involved in lipogenesis. Several enzymes play critical roles in lipogenesis, including acetyl-CoA carboxylase (ACC), which catalyzes the rate-limiting formation of malonyl-CoA, and fatty acid synthase (FASN), which catalyzes the assembly of fatty acids. Transcription factors such as SREBP1 (sterol regulatory element-binding protein 1) also regulate the expression of lipogenic genes. Cancer cells often upregulate lipogenesis, even under conditions where normal cells might rely on dietary fat. This metabolic reprogramming supports rapid cell proliferation by providing the necessary lipids for new cellular membranes and energy storage. Elevated activity of enzymes like ACC and FASN is frequently observed in tumors. High lipogenic activity in tumors has been correlated with aggressive phenotypes. Elevated expression of lipogenic enzymes is often associated with increased cell proliferation, invasion, and resistance to apoptosis. Consequently, tumors showing robust lipogenesis may be linked to poorer overall prognosis.
680-	LOX1	↑	Lectin-like oxidized low-density lipoprotein receptor 1			LOX-1 (Lectin-like oxidized low-density lipoprotein receptor 1) is a protein that has been implicated in various diseases, including cancer. Research has shown that LOX-1 is overexpressed in several types of cancer, including breast, lung, colon, and prostate cancer. LOX-1 is involved in the regulation of cell proliferation, apoptosis (cell death), and angiogenesis (the formation of new blood vessels). In cancer, LOX-1 can promote tumor growth and metastasis by: Enhancing cell proliferation and survival Inhibiting apoptosis Promoting angiogenesis Facilitating the migration and invasion of cancer cells Studies have also shown that LOX-1 can interact with other molecules involved in cancer progression, such as vascular endothelial growth factor (VEGF) and matrix metalloproteinases (MMPs). Inhibiting LOX-1 has been proposed as a potential therapeutic strategy for cancer treatment.
1299-	LPS	↑				Lipopolysaccharide (LPS) is not an endogenous protein or gene product produced by human cells, but rather a major component of the outer membrane of Gram-negative bacteria. • LPS is a potent activator of the innate immune system through receptors such as Toll-like receptor 4 (TLR4). • Its interaction with TLR4 on immune cells (e.g., macrophages, dendritic cells) and sometimes on tumor cells can trigger signaling cascades (e.g., NF-κB pathway) that result in the production of pro-inflammatory cytokines.
1005-	LRP6	↑	Low-density lipoprotein receptor–related protein 6			LRP6 (Low-density lipoprotein receptor–related protein 6) is a single-pass transmembrane co-receptor that plays an essential role in the canonical Wnt/β-catenin signaling pathway. Wnt signaling is critically involved in embryonic development, cell proliferation, differentiation, and tissue homeostasis. Dysregulation of this pathway is a well-known contributor to oncogenesis. LRP6 plays a significant role in the regulation of the Wnt/β-catenin signaling pathway—a key driver in many cancers. Its overexpression is commonly observed in various tumor types and often correlates with an aggressive clinical profile, including poor survival outcomes. These findings not only underscore the importance of LRP6 as a prognostic biomarker but also highlight its potential as a target for novel therapeutic interventions.
176-	LymphAG	↑	Lymphangiogenesis	HalifaxProj(impede)		Lymphangiogenesis is the process of forming new lymphatic vessels from pre-existing ones. Lymphangiogenesis is regulated by a range of growth factors and molecular signals, including vascular endothelial growth factor-C (VEGF-C), vascular endothelial growth factor-D (VEGF-D), and angiopoietins. Dysregulation of lymphangiogenesis has been implicated in various diseases, including cancer, lymphedema, and inflammatory disorders. Lymphangiogenesis is often upregulated in cancer, promoting the growth and spread of tumors. The expression of lymphangiogenic factors, such as vascular endothelial growth factor-C (VEGF-C) and vascular endothelial growth factor-D (VEGF-D), is increased in many types of cancer, including breast, lung, colon, and melanoma.
615-	lysoM	↝	Lysosome Membrane Integrity			Cancer cells often exhibit altered metabolism and increased autophagy to support their rapid growth and survival. Lysosomes are central to these processes, and any compromise in their integrity can disrupt cellular homeostasis. When lysosomal membranes become permeable, it can lead to the release of cathepsins (lysosomal proteases) into the cytoplasm, which can trigger apoptosis or necrosis. Loss of lysosomal membrane integrity is often associated with poor prognosis in various cancers. It can lead to increased cell survival, resistance to apoptosis, and enhanced tumor growth. Protumorigenic: Disruption of lysosomal membrane integrity is generally considered protumorigenic. It can lead to the release of cathepsins and other hydrolytic enzymes that promote tumor cell invasion, migration, and metastasis. Additionally, it can contribute to the development of a pro-inflammatory tumor microenvironment. Antitumorigenic: In some contexts, maintaining lysosomal integrity may support autophagic processes that can prevent tumorigenesis by degrading damaged organelles and proteins. However, this protective role is often compromised in cancer.
533-	lysoMP	↑	lysosomal membrane permeabilization			Different forms of stress can induce lysosomal membrane permeabilization (LMP), resulting in the translocation to the cytoplasm of intralysosomal components, such as cathepsins, inducing lysosomal-dependent cell death (LDCD). Lysosomes are single-membrane cell organelles, the main cellular function of which is to degrade extracellular material internalized by endocytosis/phagocytosis. It is now clear that lysosomes are more than a cellular “suicide bag.” Multiple pathways converge in this organelle, including endocytosis/phagocytosis, autophagy and exocytosis, and lysosomes are key players in several types of cell death. The best-studied mechanism by which LDCD is induced is ROS-mediated lysosomal destabilization Lysosomal membrane permeabilization (LMP) refers to the disruption of the lysosomal membrane, leading to the release of lysosomal contents, including hydrolytic enzymes, into the cytoplasm. This process can have significant implications for cellular homeostasis, apoptosis, and cancer biology. Lysosomal membrane permeabilization is a critical event in cancer biology, often associated with tumor progression and poor prognosis. Increased LMP can promote protumorigenic processes, while maintaining lysosomal integrity may have protective effects against cancer development.
793-	LysoPr	↑	lysosomal proteolysis			Lysosomal proteolysis is a cellular process that involves the degradation of proteins within lysosomes, which are membrane-bound organelles that contain digestive enzymes. Lysosomal proteolysis is generally considered protumorigenic. The degradation of extracellular matrix components and the release of proteolytic enzymes can facilitate tumor cell invasion and metastasis. Additionally, lysosomal proteolysis can contribute to the activation of signaling pathways that promote cell survival and proliferation.
616-	lysosome	↑	lysosome/lysosomal			Lysosomes are membrane-bound organelles that play a crucial role in cellular homeostasis by degrading and recycling various biomolecules, including proteins, lipids, and carbohydrates. They contain a variety of hydrolytic enzymes that facilitate these processes. In the context of cancer, lysosomes are increasingly recognized for their roles in tumor biology, influencing cell survival, proliferation, and metastasis. Lysosomes are generally considered protumorigenic in many contexts. Their role in degrading extracellular matrix components and releasing proteolytic enzymes can facilitate tumor cell invasion and metastasis. Additionally, lysosomes can support cancer cell survival by providing nutrients through autophagy and recycling processes.
1146-	M1	↓	M1 macrophages			M1 macrophages are classically activated, pro‑inflammatory cells that generally enhance anti‑tumor immune responses via the production of cytokines (IL‑12, TNF‑α), reactive nitrogen species (iNOS), and the expression of antigen‑presenting and costimulatory molecules (HLA‑DR, CD80, CD86). These are macrophages activated by signals such as interferon‑γ (IFN‑γ) and microbial products (e.g., lipopolysaccharide, LPS). Key Functional Attributes: -Secretion of pro‑inflammatory cytokines (e.g., TNF‑α, IL‑12, IL‑1β). -Production of reactive oxygen and nitrogen species (such as nitric oxide via inducible nitric oxide synthase, iNOS). -Promotion of Th1 adaptive immune responses, thereby enhancing anti‑tumor immunity. Role in Cancer: -In the tumor microenvironment, M1 macrophages generally are considered “anti‑tumoral” since they can mediate tumor cell killing, stimulate immune responses, and inhibit tumor progression. -However, the outcome can be context‑dependent because the balance between M1 and M2 (alternatively activated, generally pro‑tumoral) macrophages, along with other immune cells, influences the eventual prognosis. Polarized: – M1-polarized macrophages produce pro-inflammatory cytokines (e.g., TNF-α, IL-1β, IL-6, and IL-12) and generate reactive oxygen and nitrogen species. – In the tumor microenvironment, the balance between M1 (pro-inflammatory, anti-tumor) and M2 (anti-inflammatory, pro-tumor) macrophages critically shapes tumor progression. – A predominantly M1-polarized environment is generally considered to be more hostile to tumor growth, whereas M2 polarization is linked to immune suppression, tissue remodeling, and tumor progression. • M1 polarization represents a pro-inflammatory, anti-tumor state of macrophage activation characterized by robust production of cytokines and reactive species that promote tumor cell killing and support adaptive immunity. • Elevated levels of M1-polarized macrophages or a favorable M1/M2 ratio in the tumor microenvironment are generally associated with improved clinical outcomes and serve as potential prognostic indicators in a range of cancers.
177-	M2 MC	↑	M2 macrophage conversion	HalifaxProj (inhibit)		M2 macrophages (M2 MC) are a subtype of macrophages that are generally associated with anti-inflammatory responses, tissue repair, and the promotion of tumor growth. Strategies to reprogram M2 macrophages into a more pro-inflammatory M1 phenotype or to inhibit their function are being explored in cancer therapies. M2 macrophages can play a dual role, promotion/suspression. M2 macrophages are a subtype of macrophages that are generally associated with anti-inflammatory responses, tissue repair, and the promotion of tumor growth. The conversion of macrophages from the M1 (pro-inflammatory) to the M2 (anti-inflammatory) phenotype is a critical process in the tumor microenvironment and has significant implications for cancer progression. M2 macrophages are generally considered protumorigenic. They secrete various cytokines and growth factors that promote tumor cell proliferation, angiogenesis, and tissue remodeling. Additionally, they can suppress the activity of cytotoxic T cells and natural killer (NK) cells, further aiding tumor immune evasion.
178-	Macrophages	⇅	Macrophages	HalifaxProj(activate)		Macrophages are a type of white blood cell that play a crucial role in the immune system, including the response to cancer. They are derived from monocytes and can be found in various tissues throughout the body. In the context of cancer, macrophages can have both pro-tumor and anti-tumor effects, depending on their activation state and the tumor microenvironment In many tumors, macrophages are recruited to the tumor microenvironment and are referred to as tumor-associated macrophages (TAMs). Protumorigenic: Macrophages, particularly when polarized to the M2 phenotype, are generally considered protumorigenic. They can secrete cytokines, growth factors, and enzymes that promote tumor cell proliferation, angiogenesis, and tissue remodeling. Additionally, they can suppress the activity of cytotoxic T cells and natural killer (NK) cells, aiding tumor immune evasion. Antitumorigenic: Conversely, M1 macrophages (the pro-inflammatory subtype) can have antitumor effects by promoting inflammation and enhancing the immune response against tumors. They can produce pro-inflammatory cytokines and reactive oxygen species that can directly kill tumor cells.
1155-	MAD	↓	MAD proteins			MAD refers to a group of proteins that are primarily known as antagonists of MYC function. They are often categorized as members of the MAD/MXD family of transcriptional repressors, which include MAD1, MAD2 (not to be confused with the spindle assembly checkpoint protein MAD2, which is distinct), MAD3, MAD4, and related factors. These proteins generally oppose MYC activity by forming complexes that repress transcription at MYC target genes, thereby inhibiting cell proliferation and promoting differentiation. Downregulation or loss of MAD expression is often associated with poor prognosis. This is because diminished MAD activity results in enhanced MYC function, promoting aggressive tumor behavior, rapid proliferation, and often treatment resistance. -MAD protein, a late marker of oxidative stress and cell injury
852-	Mag	↓	Magnesium			Low magnesium levels have been associated with poor prognosis and increased risk of metastasis.
493-	MALAT1	↑	Metastasis Associated Lung Adenocarcinoma Transcript 1			MALAT1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is a long non-coding RNA (lncRNA) that has been implicated in various types of cancer, including lung cancer, breast cancer, and colorectal cancer. MALAT1 is often overexpressed in cancer tissues compared to normal tissues. Its expression levels have been correlated with tumor progression, metastasis, and poor prognosis in several cancers. It has been shown to promote the metastatic potential of cancer cells by regulating epithelial-mesenchymal transition (EMT) and enhancing cell migration and invasion.
472-	MAOA	↑	Monoamine Oxidase A		gene/enzyme	also known as MAO-A, or "Warrior Gene"(associated with increased aggression and impulsivity). This enzyme plays a crucial role in the breakdown of various neurotransmitters, such as serotonin, dopamine, and norepinephrine. MAOA is commonly overexpressed in prostate cancer, and others.
179-	MAP2K1/MEK1	↑	mitogen-activated protein kinase kinase 1	CGL-Driver Genes	Oncogene	MAP2K1, also known as MEK1, is a gene that encodes a protein involved in the MAPK/ERK signaling pathway, which plays a crucial role in cell proliferation, differentiation, and survival. MAP2K1 mutations are found in several types of cancer, including melanoma, lung cancer, and colorectal cancer. These mutations can lead to constitutive activation of the MAPK pathway, promoting uncontrolled cell growth and survival. MEK inhibitors, which block the activity of MEK1 and its counterpart MEK2, are being investigated in clinical trials for various cancers, particularly those with MAPK pathway alterations. MAP2K1 is found to be overexpressed, which can lead to enhanced activation of the MAPK/ERK signaling pathway. This overexpression is often associated with aggressive tumor behavior and poor prognosis. For example, elevated levels of MAP2K1 have been observed in certain types of melanoma and colorectal cancer.
180-	MAP3K1	↓	mitogen-activated protein kinase kinase kinase 1	CGL-Driver Genes	TSG	MAP3K1 (Mitogen-Activated Protein Kinase Kinase Kinase 1) is a gene that encodes a protein involved in the MAPK (Mitogen-Activated Protein Kinase) signaling pathway, which plays a crucial role in various cellular processes, including cell proliferation, differentiation, and survival. Some studies suggest that MAP3K1 may function as a tumor suppressor in certain types of cancer. Mutations or deletions in the MAP3K1 gene have been observed in various cancers, including breast cancer and melanoma, which may lead to altered signaling pathways that promote tumorigenesis. MAP3K1 interacts with other signaling pathways, including the PI3K/AKT and NF-κB pathways, which are also critical in cancer biology. This crosstalk can influence tumor growth and response to therapies.
181-	MAPK	↑	mitogen-activated protein kinase	CGL-CS		Mitogen-activated protein kinases (MAPKs) are a group of proteins involved in transmitting signals from the cell surface to the nucleus, playing a crucial role in various cellular processes, including growth, differentiation, and apoptosis (programmed cell death). MAPK Pathways: The MAPK family includes several pathways, the most notable being: 1.ERK (Extracellular signal-Regulated Kinase): Often associated with cell proliferation and survival. 2.JNK (c-Jun N-terminal Kinase): Typically involved in stress responses and apoptosis. 3.p38 MAPK: Associated with inflammatory responses and apoptosis. Inhibitors: Targeting the MAPK pathway has become a strategy in cancer therapy. For example, BRAF inhibitors (like vemurafenib) are used in treating melanoma with BRAF mutations. Altered Expression Levels: Overexpression: Many cancers exhibit overexpression of MAPK pathway components, such as RAS, BRAF, and MEK. This overexpression can lead to increased signaling activity, promoting cell proliferation and survival. Downregulation: In some cases, negative regulators of the MAPK pathway (e.g., MAPK phosphatases) may be downregulated, leading to enhanced MAPK signaling. The expression levels of MAPK pathway components can serve as biomarkers for cancer diagnosis, prognosis, and treatment response. For example, high levels of phosphorylated ERK (p-ERK) may indicate active MAPK signaling and poor prognosis in certain cancers. Numerous reports indicate that the MAPK pathway plays a major role in tumor progression and invasion, while inhibition of MAPK signaling reduces invasion.
1178-	MARK4	↑	Microtubule Affinity-Regulating Kinase 4			MARK4 is involved in phosphorylating microtubule-associated proteins. This phosphorylation modulates microtubule stability and dynamics, which are important for processes like cell division, intracellular transport, and maintaining cell structure. • Many studies have found that MARK4 is often upregulated in cancers such as breast cancer, glioma, and hepatocellular carcinoma. • Higher expression of MARK4 in these settings has been associated with a poorer prognosis, including greater tumor aggressiveness and lower survival rates.
516-	Matr	↑	matriptase			Matriptase is a member of the family of Type II transmembrane serine proteases, and has been implicated in a variety of epithelial cancers. Matriptase is a type II transmembrane trypsin-like serine protease that is expressed by cells of epithelial origin and is overexpressed in a variety of human cancers.
1206-	MATs	↑	Methionine Adenosyltransferases			tumor cells display a peculiar “methionine dependency” (i.e. an increased need for exogenous methionine), and many enzymes in methionine metabolism are dysregulated in malignancy. MAT1A,– Primarily expressed in adult liver. -decreased MAT1A expression or loss of MAT1A activity is associated with reduced production of S‐adenosylmethionine (SAM) and can contribute to malignant transformation. MAT2A -Elevated MAT2A expression is often correlated with enhanced proliferation and a worse prognosis, given its role in maintaining SAM levels in rapidly dividing tumor cells. -in cancers outside the liver, upregulation of MAT2A and methionine transporters (along with downstream effects on methylation) signify aggressive behavior and may be used as prognostic indicators. May be desireable to reduce Methionine in diet, and/or use AKBA to help reduce it, before chemo.
521-	MBD2	↑	Methyl-CpG binding domain protein 2			Mbd2 drives breast cancer progression through the modulation of epithelial-to-mesenchymal transition In many cancers, high MBD2 expression is associated with poor prognosis, indicating a more aggressive tumor phenotype and potential resistance to therapy. This is often due to its role in silencing tumor suppressor genes through DNA methylation.
182-	Mcl-1	↑	myeloid cell leukemia 1	HalifaxProj(inhibit)		a member of the Bcl-2 family of proteins, which play a crucial role in regulating apoptosis, or programmed cell death. In cancer, Mcl-1 is often overexpressed, contributing to the development and progression of various types of tumors. Mcl-1 is often overexpressed in several cancers, including hematological malignancies (like leukemia and lymphoma) and solid tumors (such as breast, lung, and prostate cancers). Mcl-1 inhibits apoptosis by binding to pro-apoptotic proteins, preventing them from triggering the cell death pathway.
990-	MCP1	↑	monocyte chemotactic protein-1			MCP-1 (Monocyte Chemoattractant Protein-1, also known as CCL2) MCP-1/CCL2 is a chemokine involved in recruiting monocytes, memory T cells, and dendritic cells to sites of inflammation. – It plays a key role in mediating immune cell trafficking, inflammation, and tissue remodeling. MCP-1 is pivotal in inflammatory responses and can modulate immune cell infiltration into tissues. – It also influences the polarization of macrophages, which may adopt pro-inflammatory (M1) or anti-inflammatory/pro-tumoral (M2) roles. Many cancers (such as breast, prostate, ovarian, lung, and colon cancers) exhibit increased levels of MCP-1. – Both tumor cells and associated stromal cells (e.g., cancer-associated fibroblasts, infiltrating immune cells) can produce MCP-1, contributing to an inflammatory milieu. • Inducers of MCP-1: – Hypoxia, oncogenic pathways, and cytokine-rich environments (e.g., IL-1β, TNF-α) can drive increased MCP-1 expression. – This upregulation often correlates with an ongoing inflammatory response in the tumor microenvironment.
743-	MCT1	↑	Multiple Copies in T-cell malignancy 1			MCT-1 is a transcriptional regulator that plays a crucial role in cell cycle regulation, apoptosis, and cell proliferation. Overexpression of MCT-1 has been observed in: Leukemia, Lymphoma, Breast, Lung, CRC
949-	MCT4	↑	Monocarboxylate Transporter 4			MCT4 is a member of the monocarboxylate transporter family, which plays a crucial role in the transport of lactate, pyruvate, and other monocarboxylates across cell membranes. In cancer, MCT4 is often upregulated to support the increased demand for lactate and pyruvate, which are essential for cancer cell metabolism. High expression of MCT4 is often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, ovarian, and glioblastoma.
1292-	MCU	↑	mitochondrial calcium uniporter			mitochondrial calcium uniporter (MCU) is a highly selective channel complex located in the inner mitochondrial membrane. -MCU facilitates the uptake of calcium (Ca²⁺) into the mitochondrial matrix, a process that is crucial for regulating mitochondrial metabolism, cell signaling, and apoptosis. -Mitochondrial Ca²⁺ uptake via MCU plays a key role in stimulating metabolic enzymes in the tricarboxylic acid (TCA) cycle, thereby influencing energy production. -Overexpression of MCU has been linked in some studies to enhanced Ca²⁺ uptake, metabolic changes, and increased tumor cell migration. -In this context, higher MCU levels (or enhanced activity) have been associated with more aggressive tumor behavior and poorer outcomes, although findings may vary with tumor subtype.
570-	MDA	↑	Serum malondialdehyde			The level of oxidative stress can be measured by assessing the MDA levels. Since MDA is highly cytotoxic and carcinogenic agent it is frequently used as a biomarker of oxidative stress during major health problems such as cancer, etc. Malondialdehyde (MDA) is the most widely used agent to estimate the extent of lipid peroxidation. Timely diagnosis of the condition followed by supplementation with antioxidants like beta-carotene, pro-vitamin A, vitamin A, vitamin C, vitamin E, lipoic acid, zinc, selenium, and spirulina can prevent potentially malignant disorders.
183-	MDM2	↑	Double Minute 2 homolog		oncoprotein	oncoprotein MDM2, a major ubiquitin E3 ligase of tumor suppressor p53; overexpression of MDM2 in human cancers is associated with a poor prognosis - A gene that encodes a protein involved in the regulation of the p53 tumor suppressor. The p53 protein plays a crucial role in controlling cell cycle progression, DNA repair, and apoptosis (programmed cell death). MDM2 functions primarily as an E3 ubiquitin ligase, which means it tags p53 for degradation, thereby regulating its levels in the cell. -MDM2 is often overexpressed in various tumors, leading to the inhibition of p53 activity. This can result in uncontrolled cell proliferation, evasion of apoptosis, and increased genomic instability, all of which contribute to tumorigenesis.
1313-	MDMX	↑	MDM4			MDMX (also known as MDM4) -MDMX, together with its homolog MDM2, is a critical negative regulator of the tumor suppressor protein p53. -MDMX is often overexpressed in multiple cancer types through gene amplification, transcriptional upregulation, or other post-transcriptional mechanisms. -Elevated MDMX levels can contribute to an environment of p53 inhibition, even in tumors that retain wild-type p53, thereby supporting cell proliferation and survival.
741-	MDR1	↑	Multidrug Resistance 1		gene	MDR-1 (Multidrug Resistance 1) is a gene that plays a crucial role in the development of resistance to chemotherapy in cancer cells. The MDR-1 gene encodes for a protein called P-glycoprotein (P-gp), which is a transmembrane efflux pump that helps to remove toxic substances, including chemotherapy drugs, from cells. MDR-1 is often overexpressed in various types of cancer, including: Leukemia, Lymphoma, Breast, Lung, Ovarian, CRC
672-	MDSCs	↑	Myeloid-derived suppressor cells			Myeloid-derived suppressor cells (MDSCs) are a type of immune cell that plays a significant role in cancer progression and immune evasion. They are a heterogeneous group of cells that are characterized by their ability to suppress the immune response, particularly the activity of T cells. MDSCs are typically found in the tumor microenvironment and are thought to be recruited to the tumor site by various factors, including tumor-derived cytokines and chemokines. Once at the tumor site, MDSCs can suppress the immune response in several ways, including: -Inhibiting the activation and proliferation of T cells -Suppressing the production of cytokines and chemokines that are necessary for an effective immune response -Inducing the production of anti-inflammatory cytokines that promote tumor growth and survival -Inhibiting the activity of natural killer (NK) cells and other immune cells that are important for tumor surveillance
522-	MeCP2	↑	Methyl-CpG-Binding Protein 2			MeCP2 is a nuclear protein that is mainly studied for its role as an epigenetic regulator of gene transcription. MeCP2, while being an epigenetic reader, also plays a role in the development and/or progression of several types of human cancer. MeCP2 is generally considered protumorigenic due to its role in promoting gene silencing through DNA methylation. By repressing the expression of tumor suppressor genes, MeCP2 can facilitate tumor growth and progression.
184-	MED12	↑	mediator complex subunit 12	CGL-Driver Genes	Oncogene	a gene that encodes a protein involved in the regulation of gene transcription. It is a component of the Mediator complex, which plays a crucial role in the transcriptional regulation of RNA polymerase II. MED12 is generally considered protumorigenic in many contexts. Its role in facilitating transcriptional activation of oncogenes and other growth-promoting factors can contribute to tumor growth and progression.
675-	MEG3	↓	Maternally Expressed Gene 3			Long non-coding RNA (lncRNA) MEG3 (Maternally Expressed Gene 3) is a tumor suppressor gene that has been implicated in various types of cancer. MEG3 is a large, non-coding RNA molecule that is normally expressed in many tissues, but its expression is often reduced or lost in cancer cells. Studies have shown that MEG3 plays a crucial role in regulating cell growth, apoptosis (programmed cell death), and angiogenesis (the formation of new blood vessels). MEG3 has been shown to inhibit the expression of oncogenes (genes that promote cancer) and to induce the expression of tumor suppressor genes. In cancer, the downregulation of MEG3 has been associated with increased cell proliferation, invasion, and metastasis. Loss of expression: Breast, lung, liver, CRC, prostate, ovarian, gastric, esophageal, pancreatic, thyroid, cervical, bladder, RCC
860-	MEK	↑	Mitogen-Activated Protein Kinase Kinase		protein kinase	MEK (Mitogen-Activated Protein Kinase Kinase) is a protein kinase that plays a crucial role in the regulation of cell growth, differentiation, and survival. MEK is often overexpressed or mutated, leading to the activation of downstream signaling pathways that promote cell growth, survival, and metastasis. MEK inhibitors have been developed as a therapeutic strategy to target cancer cells and inhibit their growth.
558-	memory	?	memory
185-	MEN1	↑	multiple endocrine neoplasia I	CGL-Driver Genes	TSG	MEN1, or Multiple Endocrine Neoplasia type 1, is a genetic disorder that affects the endocrine system and is characterized by the development of tumors in multiple endocrine glands. It is caused by mutations in the MEN1 gene, which is a tumor suppressor gene. The condition is also known as Wermer's syndrome. Individuals with MEN1 are at an increased risk for several types of tumors. The MEN1 gene, which encodes the protein menin, plays a crucial role in various cellular processes, including cell proliferation, apoptosis, and gene regulation. Loss of menin function due to mutations in the MEN1 gene can lead to uncontrolled cell proliferation and tumorigenesis. MEN I is inherently protumorigenic due to the genetic predisposition conferred by mutations in the MEN1 gene. The loss of menin function leads to dysregulation of cell growth and proliferation, contributing to the development of endocrine tumors.
638-	MET	↑	mesenchymal-epithelial-transition			Mesenchymal-epithelial transition (MET) is a process that is closely related to its counterpart, epithelial-mesenchymal transition (EMT). While EMT is a process by which epithelial cells acquire mesenchymal characteristics, MET is the reverse process, where mesenchymal cells gain epithelial properties. MET is an important process that can contribute to the development and progression of tumors. During MET, cancer cells can regain their epithelial characteristics, such as cell polarity and adhesion, which can lead to the formation of more organized and differentiated tumor structures. mesenchymal markers Vimentin (VIM), SNAIL, SLUG, and ZEB1
1319-	Mets	↓	Metallothioneins			Metallothioneins (MTs) are a family of low molecular weight, cysteine-rich proteins known primarily for their ability to bind heavy metals such as zinc, copper, cadmium, and mercury. -Owing to their high cysteine content, metallothioneins can scavenge reactive oxygen species (ROS) and mitigate oxidative stress. -Studies have investigated how inducing metallothionein expression (through dietary or pharmacological means) could offer a protective effect against carcinogens. -metallothioneins play a significant role in cellular protection mechanisms tied to detoxification and antioxidant defense, which are key elements of chemoprevention.
1087-	MGMT	↓	O^6^-methylguanine-DNA methyltransferase			MGMT (O^6^-methylguanine-DNA methyltransferase) is a DNA repair enzyme that plays a crucial role in protecting the genome from alkylating damage. Key points include: -MGMT repairs DNA lesions by removing alkyl groups from the O^6^-position of guanine, thereby preventing mutations. -It is a “suicide enzyme,” meaning that it is inactivated after repairing one lesion. -By counteracting the cytotoxic effects of alkylating agents, MGMT is a critical determinant of cell survival following exposure to such chemotherapeutic agents. In several cancers, the MGMT promoter is hypermethylated. This epigenetic modification suppresses MGMT expression and has several implications: -Reduced MGMT levels lead to an accumulation of DNA damage. -Increased mutation rates can contribute to cancer initiation and progression. MGMT expression levels in tumors have a significant impact on the response to alkylating agents (e.g., temozolomide in glioblastoma). -High MGMT Expression: Can confer resistance to these drugs by effectively repairing the induced DNA damage. -Low MGMT Expression: Often observed in tumors with MGMT promoter hypermethylation, making the cancer cells more susceptible to chemotherapeutic agents. Improved Prognosis with Low MGMT Expression in Specific Contexts (high MGMT activity can allow tumor cells to recover from DNA damage)
640-	MGO	↑	Methylglyoxal			Methylglyoxal (MGO) is a potent precursor of advanced glycosylation end-products (AGEs) Glo1 catalyzes the conversion of cytotoxic MGO to nontoxic hemithioacetal using GSH as cofactor. Because MGO rapidly forms hemithioacetal with GSH, elevated MGO will, in turn, deplete cellular GSH levels especially at low expression level of Glo2. Increased MGO, depletion of GSH and ATP are known to initiate apoptotic cell death. Some studies have investigated the potential of MGO as a therapeutic agent for cancer treatment. For example, MGO has been shown to: Enhance efficacy of chemotherapy and radiation therapy in certain types of cancer Inhibit the growth of cancer stem cells. In terms of dietary sources, MGO is found in small amounts in various foods, including: Manuka honey, which is produced by bees that gather nectar from the manuka tree, apples and grapes, onions and garlic. In many cancers, elevated levels of methylglyoxal and its associated AGEs are often linked to poor prognosis. The accumulation of these compounds can lead to increased oxidative stress, inflammation, and disruption of cellular signaling pathways. Methylglyoxal is generally considered protumorigenic due to its role in promoting the formation of AGEs, which can lead to cellular damage, inflammation, and enhanced tumor growth. MG can also induce epithelial-to-mesenchymal transition (EMT), a process associated with increased metastatic potential.
1219-	Mich	∅	Michael addition reaction.			The Michael addition reaction is a type of nucleophilic conjugate addition where a nucleophile attacks an α,β-unsaturated carbonyl compound (or, more generally, an electron-deficient alkene). This reaction is a cornerstone in organic synthesis, allowing the formation of carbon–carbon or carbon–heteroatom bonds under relatively mild conditions. -In biological systems, proteins often contain cysteine residues with thiol (-SH) groups that can act as nucleophiles. Some anticancer drug development strategies employ compounds that act as Michael acceptors. These drugs are designed to specifically form covalent bonds with cysteine residues on target proteins (such as enzymes or receptors involved in cancer cell survival). The irreversible binding can result in a prolonged inhibitory effect. Nrf2 Pathway Activation: Certain natural compounds with Michael acceptor properties (such as curcumin or specific electrophilic phytochemicals) can activate the Nrf2 (nuclear factor erythroid 2–related factor 2) pathway. -The modulation of proteins via Michael addition can indirectly affect the cellular redox state, influencing ROS levels. natural compounds known to exhibit Michael acceptor properties: -Curcumin -Sulforaphane -Parthenolide -Caffeic Acid Phenethyl Ester (CAPE) -Withania somnifera (ashwagandha) -Gambogic Acid -Dimethyl Fumarate (DMF) (resembles natural fumaric acid)
187-	MIF	↑	Macrophage Migration Inhibitory Factor	HalifaxProj(block) CGL-CF TCGA		a cytokine that plays a role in the immune response. MIF is produced by various cell types, including macrophages, and can influence the tumor microenvironment. It can promote inflammation, which is often associated with tumor progression. MIF has been shown to promote the proliferation and survival of cancer cells. It can activate signaling pathways that lead to increased cell growth and resistance to apoptosis (programmed cell death). MIF levels in the blood or tumor tissue may correlate with disease progression or poor prognosis. MIF is often overexpressed in several types of cancers, including breast, lung, colorectal, pancreatic, and gastric cancers.
1094-	MIP-1β	↑	Macrophage Inflammatory Protein‐1β			Macrophage Inflammatory Protein‐1β (MIP-1β), also known as CCL4, is a chemokine involved in recruiting and activating various immune cells such as monocytes, T lymphocytes, and natural killer (NK) cells within the tumor microenvironment. Its expression levels can influence immune cell infiltration and contribute to shaping the antitumor immune response. – MIP-1β can be secreted by tumor-associated macrophages and other immune cells within the tumor microenvironment. – Elevated levels are sometimes associated with improved immune surveillance • Dual Role: The role of MIP-1β in cancer is complex; while it promotes immune cell recruitment and may enhance antitumor immunity, in some conditions, chronic inflammation can facilitate tumor progression.
1275-	MIP‑1α	?	CCL3			CCL3 (Macrophage Inflammatory Protein-1α, MIP‑1α) -CCL3 acts as a chemoattractant for various immune cells including NK cells, dendritic cells, and monocytes. – Its role in tumors can be dual: promoting anti-tumor responses in some contexts while in others, especially through chronic inflammation, it may participate in tumor progression.
788-	MIP2	⇅	Macrophage Inflammatory Protein 2		chemokine	Macrophage Inflammatory Protein 2 (MIP-2) is a chemokine that plays a role in the recruitment of immune cells to sites of inflammation. MIP-2 is produced by various cell types, including macrophages, epithelial cells, and cancer cells themselves. It acts by binding to its receptors, CXCR1 and CXCR2, which are expressed on the surface of immune cells, such as neutrophils and macrophages.
636-	miR-125b	↑	miR-125b			miRNA-125b is a microRNA that has been extensively studied in the context of cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression by binding to the 3' untranslated region (3' UTR) of target mRNAs, leading to their degradation or inhibition of translation. miRNA-125b has been found to be involved in various types of cancer, including leukemia, breast cancer, lung cancer, and ovarian cancer. Its role in cancer is complex and can be either oncogenic (cancer-promoting) or tumor-suppressive, depending on the type of cancer and the cellular context. miR-125b is generally upregulated in various cancers, and its high expression is often associated with poor prognosis and protumorigenic effects.
766-	miR-126	↓	miR-126		tumour-suppressor miRNA	miR-126 is involved in the regulation of angiogenesis, which is the process of forming new blood vessels. miR-126 is downregulated in many types of cancer, including breast, lung, colon, and pancreatic cancer. The downregulation of miR-126 has been associated with poor prognosis and increased metastasis in cancer patients.
876-	miR-127-5p	↓	miR-127-5p		microRNA	miR-127-5p has been found to be downregulated in cancer tissues and cell lines, and its overexpression has been shown to inhibit cancer cell proliferation and induce apoptosis.
188-	MiR-1275	↑	MiR-1275			miR-1275 can act as either a tumor suppressor or an oncogene. MIR1275 gene is generally considered protumorigenic in many contexts. Its ability to produce miR-1275, which targets and downregulates tumor suppressor genes, can facilitate tumor growth, invasion, and metastasis.
782-	miR-129-5p	↓	miR-129-5p		tumor suppressor microRNA	miR-129-5p is a tumor suppressor microRNA that is downregulated in several types of cancer: breast, lung, CRC, prostate, ovarian, GC, HCC, pancreatic, Eso, Cervical, Rcc, Melanoma, GBM, Throid cancers.
705-	miR-130a	↑	miR-130a microRNA		microRNA	MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression by binding to the 3' untranslated region (3' UTR) of target mRNAs, leading to their degradation or inhibition of translation. miR-130a is overexpressed in several types of cancer: breast, lung, CRC, ovarian. key targets of miR-130a: Tp53, PTEN, SMAD4, RUNX3 miR-130a is generally considered protumorigenic in many contexts. Its ability to target and downregulate tumor suppressor genes can facilitate tumor growth, invasion, and metastasis
972-	miR-133a-3p	↓	miR-133a-3p			miR-133a-3p is a microRNA that has been implicated in various types of cancer. Downregulated in:Esophageal ,GC,BC,Lung,Ovarina (low expression=poor prognoisis) Upregulated in: HCC, RCC (associated with good prognosis)
1238-	miR-139-5p	↓			microRNA	miR-139-5p is a microRNA that plays a significant role in post-transcriptional regulation of gene expression. -miR-139-5p often targets multiple genes involved in cell cycle regulation, apoptosis, migration, and invasion. -majority of studies across various cancer types suggest that lower expressions of miR-139-5p are correlated with more aggressive tumor behaviors and poorer prognoses.
816-	miR-141	⇅	miR-141			miR-141 is a member of the microRNA-200 family, which is involved in the regulation of various cellular processes including proliferation, differentiation, apoptosis, and epithelial-to-mesenchymal transition (EMT). As a non-coding RNA, miR-141 regulates gene expression at the post-transcriptional level by binding to specific target messenger RNAs (mRNAs). miR-141 plays a role in the regulation of EMT by targeting key transcription factors or other EMT-related genes. Its regulation can thus indirectly influence cell adhesion, migration, and invasion. Both upregulation and downregulation of miR-141 have been reported, with its expression pattern often being context-dependent and linked to the stage and molecular subtype of the tumor.
651-	miR-142-3p	?	miR-142-3p microRNA			miR-142-3p is a microRNA (miRNA) that has been found to play a role in various types of cancer. MicroRNAs are small non-coding RNAs that regulate gene expression by binding to messenger RNA (mRNA) molecules and preventing them from being translated into proteins. Studies have shown that miR-142-3p can act as both a tumor suppressor and an oncogene, depending on the type of cancer. For example, in some types of leukemia, miR-142-3p is overexpressed and functions as an oncogene, promoting the growth and survival of cancer cells. On the other hand, in other types of cancer such as colorectal cancer and hepatocellular carcinoma, miR-142-3p is downregulated and functions as a tumor suppressor, inhibiting the growth and survival of cancer cells.
461-	miR-143	↓	miR-143		short RNA molecule	miR-143 and miR-145 (miR-143/145), which are located in a cluster within the 5q32-33 chromosomal region, are downregulated in many types of cancers, including colon cancer and breast cancer
839-	miR-145	↓	miR-145		tumor suppressor miRNA	miR-145 has been identified as a tumor suppressor miRNA, and its downregulation has been observed in various types of cancer
477-	miR-148a	↓	Micro RNA 148a			MiR-148a has been characterized as a tumor-suppressing miRNA and its downregulation has been reported in tumors of a variety of cancers. Identified as an oncogenic or tumor suppressor with crucial roles in the molecular mechanisms of oncogenesis.
763-	miR-155	↑	miR-155		Onco-microRNA	miR-155 has been found to be overexpressed in various types of cancer, including breast, lung, colon, and lymphoma. This overexpression has been associated with cancer progression, metastasis, and poor prognosis.
189-	miR-192-5p	↓				miR-192-5p acts as a tumor suppressor. It can inhibit the expression of oncogenes (genes that promote cancer) and is often downregulated in various types of tumors, including breast, colorectal, and liver cancers.
476-	miR-19b	↑	MicroRNA-19		oncogenic	Overexpression of miR-19 is strongly associated with cancer invasion and metastasis
902-	miR-200b	↓	miR-200b			MicroRNA-200b (miR-200b) is encoded by the MIR200B gene, which is part of the microRNA-200 family located on chromosome 1 in humans. This microRNA plays a crucial role in the regulation of gene expression, particularly in processes related to epithelial-to-mesenchymal transition (EMT), cell proliferation, differentiation, and apoptosis. miR-200b is generally considered antitumorigenic in many contexts. It plays a critical role in maintaining epithelial characteristics and inhibiting EMT, which is associated with reduced metastatic potential. By targeting genes involved in cell migration and invasion, miR-200b can suppress tumor progression
765-	miR-200c	↓	miR-200c		tumour-suppressor miRNA	miR-200c studied particularly in the regulation of epithelial-to-mesenchymal transition (EMT) and cancer metastasis. miR-200c is a member of the miR-200 family, which includes miR-200a, miR-200b, and miR-200c. These miRNAs are known to play a crucial role in maintaining epithelial cell identity and suppressing EMT, a process by which epithelial cells acquire a mesenchymal phenotype and become more migratory and invasive. miR-200c has been shown to target several genes involved in EMT and cancer progression, including: ZEB1 and ZEB2, transcription factors that promote EMT and cancer metastasis TGF-β, a cytokine that promotes EMT and cancer progression Vimentin, a protein that is highly expressed in mesenchymal cells and is associated with cancer metastasis The overexpression of miR-200c has been shown to inhibit EMT and cancer metastasis in various types of cancer, including breast, lung, and ovarian cancer. Conversely, the downregulation of miR-200c has been associated with cancer progression and poor prognosis. Downregulated in: lung, CRC, GC, pancreatic, HCC (associated with poor prognosis)
190-	miR-203	?	miR-203			miR-203 has been found to have both tumor-suppressive and oncogenic roles. miR-203 has been shown to act as a tumor suppressor. It can inhibit cancer cell proliferation, migration, and invasion by targeting oncogenes and signaling pathways that promote tumor growth. expression levels of miR-203 can vary significantly across different cancer types and stages. In some cancers, such as breast cancer and prostate cancer, miR-203 is downregulated, while in others, it may be upregulated.
511-	miR-205	⇅	microRNA 205		microRNA	miR-205 was found to be either up- or downregulated in several cancers according to the subtype, cell of origin or stage of tumor progression
191-	miR-21	↑	miR-21			miR-21 is often considered an oncogenic microRNA because its overexpression is frequently observed in many cancers. It can promote tumor growth and progression by targeting and downregulating tumor suppressor genes.
764-	miR-210	↑	miR-210		hypoxia-inducible miRNA	miR-210 is a hypoxia-inducible miRNA, meaning that its expression is increased in response to low oxygen levels (hypoxia), which is a common feature of the tumor microenvironment. miR-210 has been found to be overexpressed in various types of cancer, including breast, lung, colon, and pancreatic cancer. This overexpression has been associated with cancer progression, metastasis, and poor prognosis.
1136-	miR-215-5p	↓	miR-215-5p			– miRNA-215-5p can regulate multiple target genes involved in cell cycle control, apoptosis, migration, invasion, and differentiation. – In some studies, decreased levels of miRNA-215-5p have been associated with aggressive tumor characteristics and poorer survival, suggesting a tumor-suppressive role in those contexts. – overexpression of miRNA-215-5p may correlate with treatment resistance or more aggressive disease, indicating that its prognostic impact can be cancer type–specific.
903-	miR-218	?	miR-218
1249-	miR-22	↓	miR-22			miR-22 is a microRNA that has been widely investigated in various cancers, where it is often characterized as having tumor-suppressive functions -miR-22 predominantly acts as a tumor suppressor in multiple cancers, and its reduced expression is frequently associated with more aggressive tumor characteristics and poorer patient prognosis.
686-	miR-25-5p	↑	miR-25-5p			miR-25-5p is overexpressed in several types of cancer, including: Breast, lung, CRC, prostate targets of miR-25-5p include: TP53, PTEN, BCL2, CDKN1A
192-	miR-27a-3p	↑			oncogenic miRNA	miR-27a-3p is often found to be upregulated. It can promote tumor growth and metastasis by targeting and downregulating tumor suppressor genes.
658-	miR-29b	↓	miR-29b			miR-29b is a microRNA that has been extensively studied for its role in cancer. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to the 3' untranslated region (3' UTR) of target mRNAs, leading to their degradation or inhibition of translation. miR-29b has been found to act as a tumor suppressor in various types of cancer, including lung, breast, colon, and liver cancer. It targets several genes involved in cell proliferation, apoptosis, and metastasis, including: -Collagen genes (COL1A1, COL1A2, COL3A1), which are involved in tumor cell invasion and metastasis -Cell cycle regulators (CDK6, CCND1), which promote cell proliferation -Anti-apoptotic genes (MCL1, BCL2), which inhibit programmed cell death -Epithelial-to-mesenchymal transition (EMT) regulators (ZEB1, ZEB2), which promote tumor cell migration and invasion. Downregulation of miR-29b has been observed in various cancers, and this downregulation is often associated with poor prognosis and aggressive tumor behavior. Conversely, overexpression of miR-29b has been shown to inhibit tumor growth, induce apoptosis, and suppress metastasis in cancer cells.
737-	miR-301a-3p	↑	miR-301a-3p		microRNA	miR-301a-3p is a microRNA that has been implicated in various types of cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression by binding to the 3' untranslated region (3' UTR) of target mRNAs, leading to their degradation or inhibition of translation. miR-301a-3p is overexpressed in several types of cancer, including breast, lung, colon, and pancreatic cancer. The overexpression has been associated with cancer progression, metastasis, and poor prognosis.
728-	miR-30a-5p	↓	miR-30a-5p		microRNA	miR-30a-5p is a microRNA that has been studied for its potential role in cancer development and progression. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to messenger RNA (mRNA) and preventing its translation into protein. Downregulated in: Breast, lung, CRC, Prostate overexpression has been shown to inhibit cancer cell proliferation and migration.
746-	miR-320a	↓	miR-320a		microRNA	miR-320a is downregulated in various types of cancer, including breast, lung, colon, and prostate cancer. This downregulation is often associated with tumor progression, metastasis, and poor prognosis.
687-	miR-330-5p	↓	miR-330-5p			miR-330-5p is a microRNA that has been studied for its potential role in cancer development and progression. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by binding to messenger RNA (mRNA) and preventing its translation into protein. The mechanisms by which miR-330-5p exerts its anti-cancer effects are complex and involve the regulation of various signaling pathways, including: PI3K/AKT, MARP/ERP, WNT/β-catenin
749-	miR-340	↓	miR-340		microRNA	miR-340 is downregulated in various types of cancer, including breast, lung, colon, and prostate cancer. This downregulation is often associated with tumor progression, metastasis, and poor prognosis.
450-	miR-34a	↓	mir-34 precursor family			MiR-34a expression levels were correlated with tumor differentiation, lymphatic metastasis, clinical stages, and survival rates. miR-34a is a well-known molecule transcriptionally induced by p53 -Low miR-34a expression is common in cancers and is often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, ovarian, and glioblastoma. -High miR-34a expression is often associated with better prognosis and improved overall survival in various cancers.
775-	miR-34b-5p	↓	miR-34b-5p		tumor suppressor miRNA	miR-34b-5p is downregulated in several types of cancer: CRC, breast, lung, prostate. The tumor suppressor function of miR-34b-5p is thought to be mediated by its ability to target and downregulate genes involved in cell proliferation, survival, and metastasis. Some of the target genes of miR-34b-5p include: • BCL-2: an anti-apoptotic protein that promotes cell survival • CCND1: a cyclin-dependent kinase that promotes cell cycle progression • VEGF: a vascular endothelial growth factor that promotes angiogenesis (the formation of new blood vessels)
670-	miR-384	↓	miR-384			miR-384 is a microRNA that has been studied for its potential role in cancer development and progression. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to messenger RNA (mRNA) and preventing its translation into protein. Downregulated in: HCC, lung, CRC, gastric, pancreatic, ovarian Upregulated in: Prostate, Thyroid In many cancers, the downregulation of miR-384 is associated with increased tumor growth, invasion, and metastasis, suggesting a potential protumorigenic role when its expression is low.
698-	miR-409-3p	↓			microRNA	miR-409-3p is a microRNA that has been studied for its potential role in cancer development and progression. MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by binding to messenger RNA (mRNA) and preventing its translation into protein. miR-409-3p is downregulated in various types of cancer, including: prostate, breast, lung, CRC.
582-	miR-486	↓	miR-486			Aberrant expression of miR-486 (miR-486-5p) has been reported to be associated with different types of human cancer such as hepatocellular carcinoma (HCC), lung cancer , breast cancer , esophageal squamous cell carcinoma (ESCC) and pancreatic cancer. It can act as both the tumor suppressor and oncogene to participant in the development and progression of tumors. The down-regulation of miR-486 can promote the progression of lung cancer, HCC, breast cancer and osteosarcoma, while it is usually up-regulated in PC, chronic myeloid leukemia and gliomas. miR-486 could act as a tumor promoter by targeting CADM1 and be a potential therapeutic target for the treatment of Ovarian Cancer. : In many cancers, the downregulation of miR-486 is associated with increased tumor growth, invasion, and metastasis, suggesting a potential protumorigenic role when its expression is low.
701-	miR-497	↓				miR-497 has been identified as a tumor suppressor miRNA, and its downregulation has been observed in various types of cancer, including breast, lung, colon, and ovarian cancer. The expression of miR-497 is often reduced in cancer cells, which can lead to the upregulation of target genes involved in cell proliferation, apoptosis, and metastasis. miR-497 targets several oncogenes, including: BCL2, cyclin D1, cyclin E1, IGF1R
682-	miR-548ah-5p	⇅				miR-548ah-5p is a microRNA that has been studied in the context of various types of cancer. MicroRNAs (miRNAs) are small non-coding RNAs that play a crucial role in regulating gene expression by binding to messenger RNA (mRNA) and inhibiting its translation. Research has shown that miR-548ah-5p is involved in the regulation of several cellular processes, including cell proliferation, apoptosis, and metastasis, which are all critical in cancer development and progression. Some studies have reported that miR-548ah-5p is downregulated in certain types of cancer Downregulated: CRC, breast, lung, prostate, gastric Upregulated: HCC, ovarian, pancreatic, esophageal
726-	miR-7641	⇅	miR-7641		microRNA	miR-7641 is involved in the regulation of several cellular processes, including cell proliferation, apoptosis (programmed cell death), and metastasis. Downregulation in: breast, CRC, Ovarian, prostate, lung. Upregulation in: HCC, GC, Pancreatic.
952-	mitResp	↓	mitochondrial respiration			Mitochondrial respiration plays a crucial role in the development and progression of cancer. Cancer cells often exhibit altered metabolic profiles, including changes in mitochondrial respiration, to support their rapid growth and proliferation. In cancer cells, mitochondrial respiration is often downregulated, and instead, they rely on glycolysis for energy production, even in the presence of oxygen. This phenomenon is known as the "Warburg effect." There are several key players involved in the regulation of mitochondrial respiration in cancer cells, including: Pyruvate dehydrogenase (PDH): a critical enzyme that converts pyruvate into acetyl-CoA, which is then fed into the citric acid cycle. Citrate synthase: an enzyme that catalyzes the first step of the citric acid cycle. Succinate dehydrogenase (SDH): an enzyme that participates in both the citric acid cycle and the electron transport chain. Cytochrome c oxidase (COX): the final enzyme in the electron transport chain, responsible for generating ATP. Alterations in the expression and activity of these enzymes can impact mitochondrial respiration in cancer cells. For example, increased expression of PDH and citrate synthase can enhance mitochondrial respiration, while decreased expression of SDH and COX can impair it. Additionally, various transcription factors and signaling pathways regulate mitochondrial respiration in cancer cells, including: HIF-1α (hypoxia-inducible factor 1 alpha): a transcription factor that promotes glycolysis and suppresses mitochondrial respiration in response to hypoxia. c-Myc: a transcription factor that regulates the expression of genes involved in mitochondrial respiration and biogenesis. PI3K/Akt/mTOR: a signaling pathway that promotes cell growth and proliferation, in part by regulating mitochondrial respiration.
1010-	MKI67	↑	MKI67 (coding for the protein Ki-67)		marker	MKI67 is the gene that encodes the Ki-67 protein, a well-established marker of cellular proliferation. Ki-67 is expressed during all active phases of the cell cycle (G1, S, G2, and mitosis) but is absent in resting (G0) cells. Because of its tight correlation with cell proliferation, Ki-67 is widely used in clinical and research settings to assess the growth fraction of a given cell population, particularly in cancer. Tumors with high proliferative activity almost invariably show elevated levels of Ki-67. This increased expression is reflective of rapid cell division and active tumor growth. High Ki-67 levels are frequently associated with more aggressive tumor behavior, increased likelihood of recurrence, and poorer overall survival in many cancer types.
1017-	MKK4	⇅	Mitogen-Activated Protein Kinase Kinase 4			MKK4 (Mitogen-Activated Protein Kinase Kinase 4), also known as MAP2K4 or SEK1, is a dual-specificity kinase that plays a role in activating the stress-activated protein kinases (SAPKs) including the Jun N-terminal Kinases (JNKs) and p38 pathways. These signaling cascades are involved in cellular responses to stress, inflammation, and apoptosis. In some contexts, MKK4 is considered a tumor suppressor since its activation may trigger apoptosis or cell-cycle arrest in response to oncogenic stress. However, there are instances where increased MKK4 activity is associated with cancer progression, potentially through its roles in cell migration or by promoting a tumor-promoting inflammatory microenvironment.
1225-	MKP1	↑	MAP kinase phosphatase 1			MKP-1 and MKP-2 belong to the dual-specificity phosphatase family and are key regulators of MAPK signaling pathways (including ERK, JNK, and p38), which are central to cell proliferation, differentiation, and apoptosis. -By dephosphorylating MAPKs, these phosphatases help maintain signaling homeostasis and protect cells against excessive or prolonged MAPK activation that could lead to cell death or uncontrolled proliferation. -MKP-1 is frequently upregulated in various cancers, including breast, lung, and ovarian cancers, where it may serve as a feedback inhibitor of MAPK pathways. - In some studies, high MKP-1 levels have been linked to resistance to chemotherapy and radiotherapy, as enhanced deactivation of MAPKs can reduce apoptosis in response to treatment-induced stress.
1226-	MKP2	↑	MAP kinase phosphatase 2			MKP-1 and MKP-2 belong to the dual-specificity phosphatase family and are key regulators of MAPK signaling pathways (including ERK, JNK, and p38), which are central to cell proliferation, differentiation, and apoptosis. • By dephosphorylating MAPKs, these phosphatases help maintain signaling homeostasis and protect cells against excessive or prolonged MAPK activation that could lead to cell death or uncontrolled proliferation. - Elevated MKP-2 expression has sometimes been associated with enhanced cell survival due to dampened MAPK activity, which can contribute to tumor progression and treatment resistance.
529-	MKP5	↓	MKP5			MKPs have been shown to reverse the activation of the MAP kinases by hydrolyzing phosphothreonine and phosphotyrosine residues present in the substrates. MKP5 (Mitogen-Activated Protein Kinase Phosphatase 5) is a dual-specificity phosphatase that plays a role in regulating MAPK signaling pathways, which are critical in various cellular processes, including proliferation, differentiation, and apoptosis. MKP5 is generally downregulated in various cancers, and its low expression is often associated with poor prognosis and protumorigenic effects.
193-	MLH1	↓	mutL homolog 1, colon cancer, nonpolyposis type 2 (E. coli)	CGL-Driver Genes	TSG	MLH1 (MutL Homolog 1) is a gene that plays a crucial role in the DNA mismatch repair (MMR) system. This system is responsible for correcting errors that occur during DNA replication. Mutations or epigenetic changes in the MLH1 gene can lead to a deficiency in the mismatch repair system, which is associated with an increased risk of certain types of cancer. In many cancers, particularly those associated with Lynch syndrome, MLH1 expression may be lost due to mutations in the gene itself or through epigenetic mechanisms such as promoter methylation.
943-	MLKL	↓	Mixed Lineage Kinase Domain-Like			MLKL (Mixed Lineage Kinase Domain-Like) is a protein that plays a crucial role in necroptosis, a form of programmed cell death. MLKL is a key mediator of necroptosis, and its expression is often associated with the activation of necroptotic pathways. MLKL is often downregulated or silenced in various types of cancer. Its downregulation is often associated with tumor progression and poor prognosis.
194-	MLL2	↓	myeloid/lymphoid or mixed-lineage leukemia 2	CGL-Driver Genes	TSG	MLL2, also known as KMT2D (Lysine Methyltransferase 2D), is a gene that encodes a protein involved in the regulation of gene expression through histone methylation. MLL2 is often referred to in the context of myeloid/lymphoid or mixed-lineage leukemia 2. The term "MLL" stands for "Mixed-Lineage Leukemia," and it refers to a family of genes, including MLL (KMT2A) and MLL2 (KMT2D). MLL2 is often found to be mutated or downregulated in various cancers. These mutations can lead to a loss of function, which disrupts its role in histone methylation and gene regulation. This loss can contribute to oncogenesis by allowing the expression of oncogenes or silencing tumor suppressor genes.
195-	MLL3	↓	myeloid/lymphoid or mixed-lineage leukemia 3	CGL-Driver Genes	TSG	MLL3 (Mixed-Lineage Leukemia 3) is a gene that encodes a protein involved in the regulation of gene expression, particularly in the context of development and differentiation. It is part of the MLL family of proteins, which are known to function as histone methyltransferases, modifying chromatin structure and influencing transcriptional activity. MLL3 can act as a tumor suppressor in certain contexts, meaning that its loss or inactivation may promote cancer development. MLL3 is often considered a tumor suppressor gene. Loss-of-function mutations or deletions of MLL3 can lead to reduced expression or complete loss of the protein, which may contribute to tumorigenesis.
196-	MLPH	↓	Melanophilin	Gene		MLPH gene encodes melanophilin, a protein that helps transport melanosomes in melanocytes MLPH (Melanophilin) is a protein that plays a role in the transport of melanosomes, which are organelles responsible for the production and storage of melanin in melanocytes (the cells that produce pigment in the skin). melanophilin is generally downregulated in melanoma and potentially other cancers, and its low expression is often associated with poor prognosis and protumorigenic effects.
197-	MMP	↓	ΔΨm, mitochondrial membrane potential			destruction of mitochondrial transmembrane potential, which is widely regarded as one of the earliest events in the process of cell apoptosis. Mitochondria are organelles within eukaryotic cells that produce adenosine triphosphate (ATP), the main energy molecule used by the cell. For this reason, the mitochondrion is sometimes referred to as “the powerhouse of the cell”. Mitochondria produce ATP through process of cellular respiration—specifically, aerobic respiration, which requires oxygen. The citric acid cycle, or Krebs cycle, takes place in the mitochondria. The mitochondrial membrane potential is widely used in assessing mitochondrial function as it relates to the mitochondrial capacity of ATP generation by oxidative phosphorylation. The mitochondrial membrane potential is a reliable indicator of mitochondrial health. In cancer cells, ΔΨm is often decreased, which can lead to changes in cellular metabolism, increased glycolysis, increased reactive oxygen species (ROS) production, and altered cell death pathways.
1006-	MMP-10	↑	Matrix Metalloproteinase-10			MMP-10, also known as stromelysin-2, is a member of the matrix metalloproteinase family. These enzymes are involved in the degradation and remodeling of the extracellular matrix (ECM), which is critical for normal physiological processes such as wound healing and tissue remodeling. MMP-10 plays a significant role in cancer progression by promoting ECM degradation and remodeling, which facilitates tumor invasion, metastasis, and overall aggressiveness. Its overexpression in various cancers has been linked to poorer survival outcomes, making it a potential prognostic biomarker.
198-	MMP1	↑	Matrix metalloproteinases			MMP-1, or matrix metalloproteinase-1, is an enzyme that plays a significant role in the degradation of extracellular matrix components, particularly collagen. It is part of a larger family of matrix metalloproteinases (MMPs) that are involved in various physiological and pathological processes, including tissue remodeling, wound healing, and inflammation. MMP-1 facilitates the breakdown of the extracellular matrix, which can promote tumor invasion into surrounding tissues and the spread of cancer cells to distant sites (metastasis). By degrading collagen and other matrix components, MMP-1 can help create pathways for cancer cells to migrate. Elevated levels of MMP-1 have been associated with poor prognosis in various types of cancer, including breast, lung, and colorectal cancers. - In many cancers, high MMP-1 expression levels have been correlated with poor prognosis, indicating that it may serve as a potential biomarker for assessing tumor aggressiveness and patient outcomes.
257-	MMP1:TIMP1	↑	MMP1:TIMP1 ratio			high MMP-1/TIMP-1 ratio is linked with poor clinical outcomes. Elevated ratios correlate with increased tumor invasiveness, enhanced metastatic potential, and reduced overall survival in cancers such as breast, colorectal, and head and neck cancers. In many instances, a high MMP-1/TIMP-1 ratio has emerged as an independent prognostic factor.
608-	MMP11	↑	matrix metalloproteinase 11			a type of enzyme that plays a role in the breakdown of the extracellular matrix, a network of proteins and other molecules that provide structural support to cells and tissues. MMP11 is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. High levels of MMP11 have been associated with poor prognosis and reduced survival in cancer patients.
199-	MMP13	↑				MMP-13, or matrix metalloproteinase-13, is an enzyme that plays a significant role in the degradation of extracellular matrix components. It is involved in various physiological processes, including tissue remodeling, wound healing, and bone development. MMP-13 is often overexpressed in various types of cancers, including breast, colorectal, and lung cancers.
200-	MMP14	↑				MMP-14, also known as membrane-type matrix metalloproteinase 14 (MT1-MMP), is an enzyme that plays a significant role in the degradation of extracellular matrix components. Elevated levels of MMP-14 have been associated with poor prognosis in various cancers, including breast, colorectal, and lung cancers.
800-	MMP17	↑	Metalloproteinase 17			Metalloproteinase 17 (MMP17) is a member of the matrix metalloproteinase (MMP) family, which is a group of enzymes that play a crucial role in the degradation of the extracellular matrix (ECM). Overexpressed in: breast, lung, colon, prostate cancers
201-	MMP2	↑	metalloproteinase-2			Matrix metalloproteinase-2 (MMP-2) is an enzyme that plays a significant role in the degradation of extracellular matrix components, which is crucial for various physiological processes, including tissue remodeling, wound healing, and angiogenesis. Elevated levels of MMP-2 have been associated with poor prognosis in various cancers, including breast, lung, and colorectal cancers. MMP2 and MMP9: two enzymes are critical to tumor invasion
757-	MMP3	↑	Matrix metalloproteinase-3			MMP-3: also known as stromelysin-1, is a type of enzyme that plays a crucial role in the degradation of the extracellular matrix (ECM). MMP-3 can break down the ECM, allowing cancer cells to invade surrounding tissues and form new tumors. high levels of MMP-3 expression are associated with poor prognosis in various types of cancer, including breast, lung, and colon cancer.
202-	MMP7	↑	metalloproteinase-7			MMP-7, or matrix metalloproteinase-7, is an enzyme that plays a significant role in the degradation of extracellular matrix components. It is part of a larger family of matrix metalloproteinases (MMPs) that are involved in various physiological and pathological processes, including tissue remodeling, wound healing, and inflammation. MMP-7 can facilitate tumor invasion and metastasis by breaking down the extracellular matrix, allowing cancer cells to migrate and invade surrounding tissues. Elevated levels of MMP-7 have been associated with poor prognosis in various cancers, including colorectal, breast, and lung cancers.
203-	MMP9	↑		HalifaxProj(suppress)		Matrix metalloproteinase-9 (MMP-9) is an enzyme that plays a significant role in the degradation of extracellular matrix components. MMP-9 facilitates the breakdown of the extracellular matrix, which can enable cancer cells to invade surrounding tissues and spread to distant sites (metastasis). Elevated levels of MMP-9 have been associated with poor prognosis in several cancers, including breast, lung, and colorectal cancers. MMP2 and MMP9: two enzymes are critical to tumor invasion
1049-	MMP9:TIMP1	↑	MMP-9/TIMP-1 ratio			The balance between matrix metalloproteinase-9 (MMP-9) and its inhibitor, tissue inhibitor of metalloproteinases-1 (TIMP-1), is critical in regulating extracellular matrix remodeling. A high MMP-9/TIMP-1 ratio—reflecting either elevated MMP-9 levels, reduced TIMP-1 levels, or both—has been consistently associated with increased invasiveness, metastasis, and poorer prognosis in multiple cancer types including breast, lung, and colorectal cancers. • This ratio is being explored as a potential biomarker for tumor aggressiveness and may aid in patient stratification, treatment decision-making, and monitoring therapeutic responses. For sepsis: Although both MMP-9 and TIMP-1 levels were found equally elevated in sepsis, a decrease in the MMP-9/TIMP-1 ratio is significantly associated with severity and mortality.
204-	MMPs	↑	Matrix metalloproteinases			family of zinc-dependent proteolytic enzymes that play a key role in degrading the extracellular matrix (ECM).; are metalloproteinases that are calcium-dependent zinc-containing endopeptidases;[1] other family members are adamalysins, serralysins, and astacins. The MMPs belong to a larger family of proteases known as the metzincin superfamily.[2] MMP secretion: matrix metalloproteinase (MMP) is a kind of enzymes secreted by tumor cell to degrade ECM, facilitating the migration of tumor cells. MMPs are generally considered protumorigenic due to their role in promoting tumor invasion, metastasis, and angiogenesis. They facilitate the breakdown of the extracellular matrix, allowing cancer cells to invade surrounding tissues and spread to distant sites.
868-	MOB1	↑	MOB Kinase Activator 1			MOB1 (MOB Kinase Activator 1) is a protein that plays a crucial role in the regulation of cell growth, division, and survival. MOB1 has been shown to promote tumor growth, invasion, and metastasis by regulating the expression of genes involved in cell proliferation, survival, and migration. MOB1 has been found to be highly expressed in cancer stem cells
1076-	Mortalin	↑	mtHsp70			Mortalin (mtHsp70/HSPA9) is a chaperone protein primarily involved in mitochondrial protein import and folding. – Mortalin's interaction with p53 is a well-studied mechanism in cancer. By binding to and inactivating p53, Mortalin can prevent apoptosis and allow the survival of damaged or transformed cells. – Overexpression of Mortalin has been observed in various cancers, including breast, colon, liver, and neuroblastoma, among others. – Its elevated levels can support tumor cell proliferation, survival, and resistance to physiologic stress and chemotherapy.
1256-	motorD	?	motor function			ability to control of muscles
899-	mPGES-1	↑	Microsomal prostaglandin E synthase-1			Microsomal prostaglandin E synthase-1 (mPGES-1) is an enzyme involved in the production of prostaglandin E2 (PGE2), a pro-inflammatory mediator that plays a role in various physiological and pathological processes, including cancer. Expression is high in cancers and associated with poor prognosis and lower OS.
205-	MPL	↑	myeloproliferative leukemia virus oncogene	CGL-Driver Genes	Oncogene	gene, which encodes the thrombopoietin receptor. This receptor plays a crucial role in the regulation of hematopoiesis, particularly in the production of platelets. myeloproliferative leukemia virus oncogene (MPL) is often mutated or overexpressed in various hematological malignancies, particularly myeloproliferative neoplasms. Its expression is associated with disease progression and can influence prognosis. MPL is generally considered protumorigenic due to its role in promoting cell proliferation and survival in the context of blood cancers.
1022-	MPO	↑	myeloperoxidase (MPO)			Myeloperoxidase (MPO) is a heme-containing peroxidase most commonly associated with neutrophils and certain other myeloid cells. It plays a critical role in the innate immune response by generating reactive oxygen species (ROS) during the respiratory burst, which can destroy pathogens. MPO is predominantly expressed in neutrophils and monocytes, where it catalyzes the formation of hypochlorous acid (HOCl) and other ROS from hydrogen peroxide and chloride ions. The generation of ROS by MPO is essential for antimicrobial defense; however, these reactive molecules can also induce oxidative stress in the tumor microenvironment. MPO is not typically expressed by tumor cells themselves, but high levels can be found in tumor-infiltrating immune cells (e.g., neutrophils) or in areas of chronic inflammation.
519-	MPT	⇅	mitochondrial permeability transition			MPT refers to an alteration in the permeability of the inner mitochondrial membrane (IMM), Mitochondrial permeability transition (MPT) refers to a process involving the opening of the mitochondrial permeability transition pore (mPTP), which can lead to the loss of mitochondrial membrane potential, disruption of ATP synthesis, and release of pro-apoptotic factors into the cytosol. This process is critical in various physiological and pathological contexts, including cancer. mitochondrial permeability transition plays a significant role in cancer biology, with its dysregulation often associated with poor prognosis and protumorigenic effects. The specific roles of MPT can vary by cancer type and context
681-	MRGPRF	↑	Mas-related G-protein coupled receptor, member F			MRGPRF (Mas-related G-protein coupled receptor, member F) is a receptor that has been implicated in various physiological and pathological processes, including cancer. Research has shown that MRGPRF is overexpressed in certain types of cancer, such as breast, lung, and colon cancer. The receptor is thought to play a role in promoting tumor growth and metastasis by regulating various signaling pathways involved in cell proliferation, survival, and migration. Some studies have suggested that MRGPRF may be a potential therapeutic target for cancer treatment. For example, blocking MRGPRF with specific antagonists has been shown to inhibit tumor growth and reduce metastasis in preclinical models of cancer.
697-	MRP	↑	Multidrug Resistance-Associated Protein			MRP is a family of ATP-binding cassette (ABC) transporters that are involved in the efflux of various compounds, including chemotherapeutic agents, from cells. There are several members of the MRP family, including MRP1 (ABCC1), MRP2 (ABCC2), MRP3 (ABCC3), and others. MRP proteins are overexpressed in various types of cancer, including breast, lung, colon, and leukemia. This overexpression can lead to the efflux of chemotherapeutic agents from cancer cells, making them resistant to treatment.
424-	MRP1	↑	Multidrug Resistance Protein 1			multidrug resistance protein 1 (MRP1) encoded by ABCC1. MRP1 levels are elevated in numerous cancer types, NSCLC, breast cancer, and prostate cancer Multidrug Resistance Protein 1 (MDR1), also known as P-glycoprotein (P-gp) or ABCB1, is a membrane protein that functions as an efflux pump, transporting a variety of drugs and xenobiotics out of cells. Its expression is a significant factor in the development of multidrug resistance (MDR) in cancer therapy. Resistance Protein 1 (MDR1) is often upregulated in various cancers, and its high expression is associated with poor prognosis and protumorigenic effects due to its role in drug resistance.
1008-	MSCmark	?	MSC markers			“MSC markers” refers to the surface markers used to define and identify mesenchymal stem cells (MSCs) • The minimal criteria for mesenchymal stem cells, establishing that MSCs are plastic-adherent: - express CD105, CD73, and CD90, and -lack hematopoietic markers such as CD45, CD34, CD14/CD11b, CD19/CD79α, and HLA-DR.
1009-	MSCs	?	mesenchymal stem cells			Mesenchymal stem cells are multipotent stromal cells that can differentiate into various cell types (e.g., osteoblasts, adipocytes, chondrocytes). MSCs are of interest because—beyond their role in tissue repair and immunomodulation—they are implicated in the tumor microenvironment. MSCs can interact with cancer cells, and there is evidence that they can influence tumor growth, metastasis, and drug resistance.
207-	MSH2	↓	mutS homolog 2, colon cancer, nonpolyposis type 1 (E. coli)	CGL-Driver Genes	TSG	MSH2 (MutS Homolog 2) is a gene that plays a crucial role in the DNA mismatch repair (MMR) system. This system is responsible for correcting errors that occur during DNA replication, such as base-base mismatches and insertion-deletion loops. When the MSH2 gene is mutated or dysfunctional, it can lead to an accumulation of genetic errors, which increases the risk of developing certain types of cancer. Tumors that exhibit a deficiency in mismatch repair (dMMR), often due to the loss of MSH2 and other MMR proteins, are characterized by a high level of microsatellite instability (MSI).
208-	MSH6	↓	mutS homolog 6 (E. coli)	CGL-Driver Genes	TSG	MSH6 is a gene that plays a crucial role in the DNA mismatch repair (MMR) system, which is responsible for correcting errors that occur during DNA replication. Mutations in the MSH6 gene can lead to a deficiency in this repair mechanism, resulting in an increased risk of certain types of cancer, particularly those associated with Lynch syndrome (also known as hereditary nonpolyposis colorectal cancer, or HNPCC). In many cancers associated with MSH6 mutations, there is often a loss of expression of the MSH6 protein.
1266-	Mst1	↓	Mammalian Ste20-like kinase 1			MST1 (Mammalian Ste20-like kinase 1), also known as STK4, is a key component of the Hippo signaling pathway and has been implicated in regulating cell proliferation, apoptosis, and tissue homeostasis. Several studies have suggested that MST1 expression may be reduced in aggressive breast cancer subtypes. • Prognosis: Lower MST1 levels have been associated with enhanced tumor growth and metastasis, suggesting a potential tumor suppressor role. Some reports correlate low MST1 with poorer disease-free and overall survival.
614-	mtDam	?	mitochondrial damage			Mitochondrial damage can lead to a shift from oxidative phosphorylation to glycolysis, a process known as the Warburg effect. This shift can provide cancer cells with a selective advantage, allowing them to grow and proliferate more rapidly. Mitochondrial Damage can also lead to cell death of cancer cells.
209-	mTOR	↑	mammalian target of rapamycin	HalifaxProj (inhibit)		mTOR (mechanistic target of rapamycin) is a central regulator of cell growth, proliferation, metabolism, and survival. It is a serine/threonine kinase that integrates signals from nutrients, growth factors, and cellular energy status. mTOR promotes protein synthesis and cell growth by activating downstream targets such as S6 kinase and 4E-BP1. In cancer, this pathway can become hyperactivated, leading to uncontrolled cell proliferation. mTor Inhibitors: -rapamycin (Sirolimus): classic natural product mTOR inhibitor -Curcumin -Resveratrol -Epigallocatechin Gallate (EGCG) -Honokiol
440-	mTORC1	↑	mammalian target of rapamycin complex 1			crucial signaling node that integrates environmental cues to regulate cell survival, proliferation, and metabolism, and is often deregulated in human cancer. Activation of mTOR signaling is associated with oncogenic cellular processes, making mTOR a promising target for treating multiple hallmarks of the cancer phenotype.
441-	mTORC2	↑	mammalian target of rapamycin (mTOR) complex 2			mTORC2 associates closely with the plasma membrane, and has been detected in association with ribosomal membranes (11), where it can interact with its key substrates, the AGC kinases including AKT1-3, serum glucose kinase (SGK) isoforms, and protein kinase C (PKC) family members. Rapamycin is a known allosteric inhibitor of mTORC1, while TOR kinase inhibitors (TOR-KIs) inhibit the activities of both complexes. AKT, a key substrate of mTORC2, is among the most commonly hyper-activated proteins in cancer. AKT integrates signals from PI3K/mTORC2 and from PI3K/PDK1 to promote cell growth and survival.
206-	MUC1	↑	Mucin 1		oncoprotein	The mucin 1 (MUC1) heterodimeric oncoprotein is overexpressed in human prostate cancers with aggressive pathologic and clinical features, resulting in a poor MUC1 (Mucin 1) is a glycoprotein that is expressed on the surface of epithelial cells and plays a role in cell signaling, protection, and lubrication. It is also involved in various biological processes, including cell adhesion and immune response outcome. MUC1 is often overexpressed in various types of cancers, including breast, ovarian, pancreatic, and colorectal cancers.
971-	MUC1-C	↑				MUC1-C is a truncated form of the MUC1 protein that is generated through alternative splicing. MUC1-C lacks the extracellular domain of MUC1 and is instead localized to the cytoplasm and nucleus. MUC1-C has been shown to have distinct functions from MUC1, including the regulation of cell growth, survival, and transformation. MUC1-C is often overexpressed in cancer cells and can contribute to oncogenesis by promoting cell proliferation, inhibiting apoptosis, and enhancing metastasis.
611-	MUC4	↑	mucin, a high-molecular-weight glycoprotein			plays a crucial role in protecting and lubricating the epithelial surfaces of various organs, including the respiratory, gastrointestinal, and reproductive tracts. MUC4 has been found to be overexpressed in several types of tumors, including pancreatic, ovarian, lung, breast cancers and strongly expressed in Gastric Cancers. This overexpression has been associated with tumor progression, metastasis, and poor prognosis.
210-	Myc	↑	v-myc avian myelocytomatosis viral oncogene homolog	TCGA		Myc is a family of regulator genes and proteins that play a crucial role in cell cycle progression, apoptosis, and cellular transformation. Myc is often found to be overexpressed or dysregulated in many types of tumors. This overexpression can lead to uncontrolled cell division and growth, contributing to the development and progression of cancer. Myc is frequently overexpressed in various cancers, including hematological malignancies (like Burkitt lymphoma) and solid tumors (such as breast, lung, and colon cancers). This overexpression can result from genetic alterations, such as chromosomal translocations, amplifications, or mutations.
564-	MyD88	↑	Myeloid differentiation factor 88	CGL-Driver Genes	Oncogene	a gene that encodes a cytosolic adapter protein necessary for both innate and adaptive immune response. The expression of MyD88 is elevated in tumor tissues compared to normal tissues, such as those found in breast, lung, liver, colon, and stomach organs. Researchers have drawn contradictory conclusions regarding the role of MyD88 therein. The reason may be, on one hand, inhibiting MyD88 may weaken immune function, resulting in compromised immune surveillance against tumor cells and a reduced ability to eliminate pathogenic factors. This scenario can promote the emergence and progression of tumors. On the other hand, suppressing MyD88 might alleviate inflammation, thus preventing inflammation-associated tumorigenesis. MYD88 (myeloid differentiation primary response 88) is a key adaptor protein involved in the signaling pathways of the immune system, particularly in the Toll-like receptor (TLR) and interleukin-1 receptor (IL-1R) pathways. Elevated MYD88 expression or the presence of MYD88 mutations can be associated with poor prognosis in certain cancers.
355-	N-cadherin	↑	N-cadherin			also known as Cadherin2 (CDH2) N-cadherin is a type of cell adhesion molecule that plays a crucial role in the development and maintenance of tissue structure. In the context of cancer, N-cadherin has been implicated in the progression and metastasis of various types of tumors. N-cadherin expression is increased in various types of cancer Normally, N-cadherin is expressed in mesenchymal cells, such as fibroblasts and smooth muscle cells. However, in cancer cells, N-cadherin expression is often upregulated, which can contribute to the epithelial-to-mesenchymal transition (EMT). EMT is a process by which epithelial cells acquire a more mesenchymal phenotype, which is characterized by increased motility, invasiveness, and resistance to apoptosis. The expression of N-cadherin in cancer cells is closely associated with tumorigenesis and metastasis. Additionally, the soluble N-cadherin level in the serum of cancer patients is much higher than that in the serum of healthy patients, revealing a positive relation with poor prognosis.
357-	n-MYC	↑	n-MYC Oncogene		Oncogene	The MYC proto-oncogenes are among the most commonly activated proteins in human cancer. N-myc is primarily implicated in high-grade neuroendocrine tumors (neuroblastoma and small-cell carcinomas) and those arising from the neural system (neuroblastoma, medulloblastoma, and glioblastoma). Overexpression is generally associated with a more aggressive clinical course and lower survival rates.
0-	NA	?	NA	NA	NA	NA
815-	NAD	↓	Nicotinamide adenine dinucleotide		coenzyme	NAD generally refers to the oxidized form, known as NAD⁺ NAD (Nicotinamide adenine dinucleotide) is a coenzyme that plays a crucial role in various cellular processes, including energy metabolism, DNA repair, and cell signaling. Research has shown that NAD levels are often decreased in cancer cells, and this decrease can contribute to the development and progression of cancer. NAD is a coenzyme that plays a central role in energy metabolism, DNA repair, and cell signaling. It exists in two forms: NAD+ (oxidized) and NADH (reduced). NADH is the reduced form of NAD⁺. When NAD⁺ accepts electrons (typically during metabolic processes like glycolysis, the citric acid cycle, and beta-oxidation), it becomes NADH. NADPH, on the other hand, is a phosphorylated form of NADP+, which is a related coenzyme. NADPH is primarily involved in anabolic reactions, such as fatty acid synthesis, cholesterol synthesis, and antioxidant defenses.
1120-	NADH	↑	Nicotinamide Adenine Dinucleotide			NADH is the reduced form of NAD⁺, meaning it has accepted electrons (and usually a proton) during metabolic reactions. When NAD⁺ accepts electrons (typically during metabolic processes like glycolysis, the citric acid cycle, and beta-oxidation), it becomes NADH. -By influencing the balance between NADH and NAD⁺, ENOX2 might shift the cellular redox state. An imbalance can lead to increased oxidative stress or changes in ROS signaling pathways. • The ratio between NADH and NAD⁺ is a key indicator of a cell’s metabolic state. • Some studies have suggested that abnormal NADH metabolism or shifts in the NADH/NAD⁺ ratio can be correlated with tumor aggressiveness or response to therapy. • For example, in certain cancers, a higher NADH/NAD⁺ ratio may be associated with more aggressive behavior, resistance to apoptosis, or poor prognosis.
1121-	NADH:NAD	↑	NADH:NAD+ ratio			The ratio between NADH and NAD⁺ is a key indicator of a cell’s metabolic state. • In many cancers, changes in this ratio may indicate increased reliance on glycolysis or alterations in mitochondrial function. • Some studies have suggested that abnormal NADH metabolism or shifts in the NADH/NAD⁺ ratio can be correlated with tumor aggressiveness or response to therapy. • For example, in certain cancers, a higher NADH/NAD⁺ ratio may be associated with more aggressive behavior, resistance to apoptosis, or poor prognosis. A shift toward a higher NADH/NAD⁺ ratio can potentially impair these regulatory pathways, diminishing the cell’s capacity to respond to or repair damage from elevated ROS levels. -a high NADH/NAD⁺ ratio can lead to increased ROS production, particularly through mitochondrial electron leakage.
853-	NADHdeh	⇅	NADH dehydrogenases		enzymes	NAD-dehydrogenases, also known as NADH dehydrogenases or NADH:quinone oxidoreductases, are a group of enzymes that play a crucial role in the electron transport chain (ETC) of mitochondria. These enzymes are responsible for catalyzing the transfer of electrons from NADH to the electron transport chain, ultimately contributing to the generation of ATP (adenosine triphosphate) during cellular respiration. Complex I (NADH dehydrogenase): This is the largest and most complex enzyme in the electron transport chain, consisting of 45 subunits. It is responsible for transferring electrons from NADH to the electron transport chain. NADH stands for Nicotinamide Adenine Dinucleotide (in its reduced form). It is a vital coenzyme found in all living cells, primarily involved in redox (oxidation–reduction) reactions. In its reduced form (NADH), it carries electrons that are used in various metabolic pathways, including ATP production in the mitochondrial electron transport chain. NAD-dehydrogenases play a crucial role in the generation of ATP during cellular respiration. NAD-dehydrogenases help regulate the redox state of the cell by controlling the levels of NADH and NAD+. NAD-dehydrogenases can also function as antioxidants, helping to protect the cell from oxidative damage. NADH is the substrate (electron donor), NADH dehydrogenases are the enzymes that help process NADH by removing its electrons.
624-	NADPH	↑	Nicotinamide adenine dinucleotide phosphate			NADPH (Nicotinamide adenine dinucleotide phosphate) is a crucial molecule in cellular metabolism, playing a key role in various biological processes, including energy production, antioxidant defenses, and biosynthesis. NADPH is essential for the proper functioning of the pentose phosphate pathway, which generates NADPH and ribose-5-phosphate. Cancer cells may exploit this pathway to support their high energy demands. Many types of cancer, including breast, lung, and colon cancer, exhibit increased NADPH levels compared to normal tissues. This increase is often associated with enhanced glucose-6-phosphate dehydrogenase (G6PD) activity, a key enzyme in the pentose phosphate pathway that generates NADPH.
625-	NADPH/NADP+	↑	NADPH/NADP+ ratio			The NADPH/NADP+ ratio is a crucial indicator of cellular redox status and has been implicated in various diseases, including cancer. NADPH (Nicotinamide adenine dinucleotide phosphate) is a reducing agent that plays a central role in maintaining the balance of redox reactions within cells. In cancer cells, the NADPH/NADP+ ratio is often altered
917-	NAF1	↑	Neutrophil-activating factor 1			Neutrophil-activating factor 1 (NAF-1), also known as NAF1 or Cisd2, is a mitochondrial protein that plays a crucial role in regulating cellular iron homeostasis and reactive oxygen species (ROS) production. High NAF-1 expression is generally associated with poor prognosis in various types of cancer.
1019-	NAIP	⇅	Neuronal Apoptosis Inhibitory Protein			NAIP (Neuronal Apoptosis Inhibitory Protein) is a member of the inhibitors of apoptosis (IAP) family and is implicated in the regulation of cell death, as well as in innate immune responses. NAIP is primarily known for its ability to inhibit apoptosis by interfering with caspase activation, which helps cells survive under stress conditions. In some cancers, elevated NAIP levels may contribute to tumor cell survival by inhibiting apoptosis, thereby supporting tumor progression. Conversely, in other settings, NAIP expression might be part of an innate immune response activated within the tumor, which could have implications for anti-tumor immunity.
212-	Nanog	↑	human hNanog protein coded by the NANOG gene			NANOG is a transcription factor in embryonic stem cells (ESCs); Nanog is one of the key transcription factors, along with Oct4 and Sox2, involved in maintaining pluripotency in embryonic stem cells.’ Increased expression of Nanog has been associated with the aggressive nature of certain cancers, highlighting its role in promoting cancer stem cell characteristics.; Nanog's role in metastasis includes promoting the survival and proliferation of cancer stem cells in secondary sites, aiding their ability to establish new tumors. Nanog is often expressed in cancer stem cells (CSCs), High levels of Nanog expression have been correlated with increased tumor aggressiveness, metastasis, and the ability to evade apoptosis (programmed cell death).
703-	NBR2	↑	long noncoding RNA neighbor of BRCA1 lncRNA 2		long noncoding RNA	NBR2 (Neighbor of BRCA1 gene 2) is a protein that has been associated with various cellular processes, including cell cycle regulation, DNA repair, and apoptosis. Research has shown that NBR2 may play a role in cancer development and progression. Studies have found that NBR2 is overexpressed in several types of cancer, including breast, ovarian, and lung cancer. This overexpression has been linked to increased cell proliferation, tumor growth, and metastasis.
790-	NCAM	↑	Neural Cell Adhesion Molecule			NCAM (Neural Cell Adhesion Molecule) is a cell surface glycoprotein that plays a crucial role in cell-cell adhesion, migration, and signaling. NCAM expression has been linked to increased tumor aggressiveness and poor prognosis in various cancer types, including breast, lung, and colon cancer.
985-	NCOA4	?	Nuclear Receptor Coactivator 4			NCOA4 (Nuclear Receptor Coactivator 4) is a protein that was initially characterized as a coactivator for nuclear receptors, enhancing transcriptional activity in response to ligands such as hormones. Beyond transcriptional coactivation, NCOA4 is also known for its role in selective autophagy, particularly in mediating ferritinophagy (the autophagic degradation of ferritin), thus influencing cellular iron homeostasis. Dysregulation of NCOA4 and its impact on iron metabolism may contribute to tumor progression, where a delicate balance between proliferation and cell death is maintained.
213-	NCOR1	?	nuclear receptor co-repressor 1	CGL-Driver Genes	TSG	a protein that plays a critical role in the regulation of gene expression by interacting with nuclear receptors and other transcription factors. It is involved in various cellular processes, including development, metabolism, and differentiation. potential tumor suppressor in some cancers and its involvement in oncogenic processes in others.
166-	NDRG1	↓	N-myc Downstream Regulated Gene 1			NDRG1 functions as a modulator of cell differentiation and has been linked to cellular responses to stress and hypoxia. It is involved in multiple signaling pathways and can influence processes such as cell cycle regulation, apoptosis, and metastasis. In several cancer types, high NDRG1 expression has been correlated with better clinical outcomes, such as lower incidence of metastasis and improved overall survival. This is consistent with its proposed function as a metastasis suppressor.
944-	Necroptosis	⇅	Necroptosis		type of cell death	Necroptosis, is a form of programmed cell death that is regulated by the cell's own mechanisms. It is a form of cell death that is mediated by specific signaling pathways, including the RIP1-RIP3-MLKL pathway. Necroptosis is characterized by the activation of specific enzymes, such as RIP1 and RIP3, which lead to the formation of a necroptotic complex that ultimately causes cell death. necroptosis expression can be elevated in certain types of cancer, it can also be reduced in other types of cancer.
781-	necrosis	?	necrosis		type of cell death	Necrosis is a type of cell death that occurs when cells are damaged or injured, leading to the loss of cellular homeostasis and the eventual death of the cell. Necrosis is a non-programmed form of cell death, meaning that it is not a deliberate or controlled process, but rather a response to cellular damage or injury.
527-	NEDD9	↑	Neural precursor cell expressed developmentally down-regulated protein 9			NEDD9 (Neural Precursor Cell Expressed Developmentally Downregulated 9) is a protein that has been implicated in various cellular processes, including cell adhesion, migration, and signaling. It is part of the CAS (Crk-associated substrate) family of proteins and is known to interact with several signaling pathways, particularly those involving integrins and growth factor receptors. NEDD9 is often found to be overexpressed in various types of cancers, including breast, lung, and colorectal cancers. This overexpression is associated with more aggressive tumor behavior and poorer prognosis. NEDD9 interacts with several signaling pathways, including those mediated by epidermal growth factor receptor (EGFR) and other receptor tyrosine kinases. These interactions can enhance signaling pathways that promote cell survival, proliferation, and migration.
1024-	Nestin	↑	Nestin			Nestin is an intermediate filament protein originally identified in neural stem cells. High nestin expression is frequently observed in glioblastoma and other high-grade brain tumors. – Its expression is associated with tumor stem cell populations that contribute to therapy resistance and tumor recurrence. High nestin expression is generally correlated with poorer prognosis, including reduced overall survival and higher recurrence rates. – In several tumor types, nestin is considered a marker of high malignancy and aggressive behavior.
13-	Netrins	↑	Netrins			Netrins genes encode a family of secreted and membrane‐associated proteins that function as chemotropic guidance signals for directing cell and axon migration throughout nervous system development. Netrin-1 is upregulated in a large fraction of cancers. The expression of Netrin-1 is markedly reduced or absent in ~50% of brain tumors and prostate cancer, while it is overexpressed in many other cancers. Netrin family consists primarily of secreted proteins (e.g., Netrin‑1, Netrin‑4) and their receptors (such as DCC [Deleted in Colorectal Cancer] and UNC5 homologues) that guide axonal migration and cell positioning during development. Their roles in cancer are complex and context‑dependent, with some family members acting as tumor promoters and others behaving in a tumor‑suppressive manner.
1255-	neuroG	?	neurogenesis			Neurogenesis is the process by which nervous system cells, the neurons, are produced by neural stem cells.
1100-	Neurog1	↑	Neurogenin 1			Neurog1 is a basic helix-loop-helix (bHLH) transcription factor known primarily for its role in neuronal differentiation. • In neuroblastoma and certain CNS tumors like gliomas and medulloblastomas, higher expression of neural differentiation markers—including Neurog1—can sometimes hint at a more differentiated (and potentially less aggressive) tumor phenotype, but this is not universal.
1105-	neuroP	↓	neuroprotective			neuroprotective refers to the ability of a substance, intervention, or strategy to preserve the structure and function of nerve cells (neurons) against injury or degeneration. -while cancer and neurodegenerative processes might seem distinct, there is significant overlap in terms of treatment-related neurotoxicity, shared molecular mechanisms, and the potential for therapies that provide neuroprotection during cancer treatment.
610-	NeuroT	↑	neurotensin			a peptide hormone found in the brain and gastrointestinal tract. It plays a role in various physiological processes, including pain modulation, cardiovascular regulation, and gastrointestinal motility. Neurotensin expression has been observed in various types of cancer, and its levels can be correlated with tumor progression, metastasis, and patient prognosis. Overexpressed in: Breast, Pancreatic, lung, Colorectal, Prostate, Ovarian.
910-	Neut	↑	neutrophils		white blood cell	Neutrophils are a type of white blood cell that plays a crucial role in the immune system. They are involved in the defense against infections and inflammation. High levels of neutrophils in the tumor microenvironment have been linked to poor prognosis in various types of cancer, including breast, lung, and colon cancer.
214-	NF-kB	↑	Nuclear factor kappa B	HalifaxProj(inhibit)		NF-kB signaling Nuclear factor kappa B (NF-κB) is a transcription factor that plays a crucial role in regulating immune response, inflammation, cell proliferation, and survival. NF-κB is often found to be constitutively active in many types of cancer cells. This persistent activation can promote tumorigenesis by enhancing cell survival, proliferation, and metastasis.
215-	NF1	↓	neurofibromin 1	CGL-Driver Genes	TSG	The NF1 gene, located on chromosome 17, encodes the neurofibromin protein, which is a tumor suppressor. Neurofibromin plays a critical role in regulating cell growth and differentiation, particularly in the nervous system. Neurofibromin acts as a tumor suppressor by negatively regulating the Ras signaling pathway. When NF1 is expressed normally, it helps control cell proliferation and survival. Loss or reduction of NF1 expression can lead to increased Ras activity, promoting uncontrolled cell growth and tumorigenesis.
216-	NF2	↓	neurofibromin 2 (merlin)	CGL-Driver Genes	TSG	The NF2 gene, located on chromosome 22, is crucial for the regulation of cell growth and the maintenance of cellular structures. It encodes a protein called merlin (or schwannomin), which acts as a tumor suppressor.
587-	NFAM1	↑	Neural Factor Activating Mast cells 1			NFAM1 (Neural Factor Activating Mast cells 1) is a protein that interacts with ITAM1 (Immunoreceptor Tyrosine-based Activation Motif 1). NFAM1 is a member of the Fc receptor gamma chain (FcRγ) family, which is a group of proteins that play a crucial role in the activation of immune cells, such as mast cells and basophils. NFAM1 has been shown to be overexpressed in breast cancer tissues, particularly in triple-negative breast cancer (TNBC) and HER2-positive breast cancer, non-small cell lung cancer (NSCLC), Leukemia, and Melanoma. • Immune evasion: NFAM1 may help cancer cells evade the immune response by inhibiting the activation of immune cells, such as T cells and natural killer cells. • Cell proliferation and survival: NFAM1 may promote cell proliferation and survival by activating signaling pathways that regulate cell growth and survival. • Angiogenesis: NFAM1 may promote angiogenesis, the formation of new blood vessels, which is essential for tumor growth and metastasis.
586-	NFAT	↑	nuclear factor of activated T cells			(NFAT) is a family of transcription factors that play a crucial role in the regulation of gene expression in various cell types, including immune cells and cancer cells. NFAT proteins are involved in the regulation of cell growth, differentiation, and survival, and their dysregulation has been implicated in the development and progression of cancer. NFAT family: NFAT1, NFAT2, NFAT3, NFAT4, and NFAT5. Cell proliferation: NFAT proteins can regulate the expression of genes involved in cell cycle progression and cell growth, which can contribute to the development of cancer. • Angiogenesis: NFAT proteins have been implicated in the regulation of angiogenesis, the process of new blood vessel formation, which is essential for tumor growth and metastasis. • Metastasis: NFAT proteins can regulate the expression of genes involved in cell migration and invasion, which can contribute to the development of metastatic disease. • Immune evasion: NFAT proteins can regulate the expression of genes involved in immune evasion, which can allow cancer cells to evade the immune system. Studies have shown that NFAT proteins are overexpressed in several types of cancer, including breast, lung, and colon cancer.
217-	NFE2L2	↑	nuclear factor (erythroid-derived 2)-like 2	CGL-Driver Genes	Oncogene	a transcription factor that plays a crucial role in cellular defense mechanisms against oxidative stress and inflammation. It regulates the expression of various antioxidant and detoxifying enzymes, helping to protect cells from damage caused by reactive oxygen species (ROS) In many cancers, NRF2 is found to be constitutively activated due to mutations in the NFE2L2 gene or alterations in its regulatory pathways.
218-	NH3	↑	ammonia			Cancer cells can produce ammonia through processes like glutaminolysis, where glutamine is metabolized to support rapid growth and proliferation. High levels of ammonia can suppress the function of certain immune cells, such as T cells and natural killer (NK) cells, potentially allowing tumors to evade immune surveillance.
474-	NHE1	↑	Na+/H+ exchanger isoform 1			plays a crucial role in cancer cell proliferation and metastasis. NHE1 is a ubiquitously expressed acid-extruding membrane transport protein, and upregulation of its expression and/or activity is commonly correlated with tumor malignancy.
1270-	NHE3	⇅	Sodium/Hydrogen Exchanger 3			NHE3 (Sodium/Hydrogen Exchanger 3), encoded by the SLC9A3 gene, is best known for its role in maintaining sodium and fluid balance as well as intracellular pH, particularly in epithelial tissues such as the intestine and kidney. -well known that NHE3 activity is increased with PI3K cascade activation • NHE3 is central to regulating the intracellular pH by exchanging intracellular H⁺ for extracellular Na⁺. • By controlling pH and ion balance, NHE3 indirectly contributes to cell volume regulation, nutrient absorption, and overall epithelial barrier integrity. • In non-transformed tissues, NHE3 activity supports normal metabolic functions and cellular homeostasis. Expression in Cancer • Tumor Microenvironment: Cancer cells often face an acidic microenvironment; alterations in NHE activity (including NHE3) could help tumor cells adapt by regulating intracellular pH. -The degree of NHE3 expression (upregulation or downregulation) may vary with cancer type and the specific tumor microenvironment, influencing local pH balance and, consequently, tumor behavior.
219-	NK cell	?	NK cell activity	HalifaxProj(promote)		Natural Killer (NK) cells are a type of lymphocyte in the immune system that play a crucial role in the body's defense against tumors and virally infected cells. NK cells can directly kill cancer cells through the release of cytotoxic granules containing perforin and granzymes. Perforin forms pores in the target cell membrane, allowing granzymes to enter and induce apoptosis (programmed cell death). NK cells produce various cytokines, such as interferon-gamma (IFN-γ), which can enhance the immune response and promote the activation of other immune cells, including macrophages and T cells. -Monoclonal Antibodies: Using antibodies that engage NK cells to target and kill cancer cells. -Cytokine Therapy: Administering cytokines like IL-2 or IL-15 to boost NK cell activity.
699-	NKD2	↓	Naked cuticle homolog 2		protein	NKD2 is a negative regulator of the Wnt/β-catenin signaling pathway, which is involved in various cellular processes, including cell proliferation, differentiation, and survival. NKD2 has been identified as a tumor suppressor gene, and its expression is often downregulated in various types of cancer: CRC, breast, lung, Prostate, ovarian
1104-	NKG2D	⇅	natural killer group 2, member D (NKG2D) ligands			“NKG2D” itself is a receptor on immune cells, and most research focuses on its ligands—such as MICA, MICB, and the UL16-binding proteins (ULBPs)—that are expressed by tumor cells or within the tumor microenvironment. MICA and MICB • Expression: – Frequently overexpressed on the surface of transformed cells in cancers such as colorectal, ovarian, breast, and pancreatic cancers. • Prognosis: – In some studies, high levels of MICA/B on tumor cells have been correlated with enhanced NK cell-mediated lysis and better prognosis. 2. ULBPs (ULBP1, ULBP2, ULBP3, etc.) -Overexpression of certain ULBP family members has been associated with increased tumor recognition by NK and CD8⁺ T cells, potentially correlating with improved survival in some studies (e.g., ovarian cancer). – In contrast, increased soluble ULBP levels have been linked to immune evasion and worse outcomes in other contexts.
387-	NKX3.1	↓	Homeobox protein Nkx-3.1			NKX3.1 is a prostatic tumor suppressor gene located on chromosome 8p. Commonly down-regulated in human prostate cancer. NKX3.1 is a homeobox transcription factor that is normally highly expressed in prostate luminal epithelial cells. – During prostate tumorigenesis, NKX3.1 expression is frequently downregulated or lost, particularly in higher-grade lesions and advanced disease. Reduced or absent NKX3.1 expression is generally associated with poor prognosis.
908-	NLRP3	↑	NOD-like receptor pyrin domain-containing protein 3			NLRP3 (NOD-like receptor pyrin domain-containing protein 3) is a protein that plays a crucial role in the regulation of inflammation and immune responses. NLRP3 typically has high expression in cancers, with poor prognosis.
404-	NM23	↓	NM23			NM23 is a metastasis suppressor gene. Reductions in Nm23-H1 expression have been significantly associated with aggressive behavior in gastric carcinoma, ovarian cancer, melanoma, and breast cancer. NM23 genes are typically expressed in many tissues under normal conditions. – In several cancers, particularly metastatic tumors, the expression of NM23 (especially NM23-H1) can be reduced compared to primary tumors, consistent with its role as a metastasis suppressor. Low NM23 expression has been associated with increased metastatic potential in cancers such as breast, melanoma, and hepatocellular carcinoma. – In these contexts, decreased NM23 levels often correlate with a poorer prognosis and enhanced tumor aggressiveness.
695-	NNMT	↑	Nicotinamide N-methyltransferase		enzyme	NNMT (Nicotinamide N-methyltransferase) is an enzyme that has been implicated in various diseases, including cancer. Research has shown that NNMT is overexpressed in several types of cancer, such as breast, lung, and colon cancer. NNMT is involved in the metabolism of nicotinamide, a form of vitamin B3. The enzyme catalyzes the transfer of a methyl group from S-adenosylmethionine (SAMe) to nicotinamide, resulting in the formation of N-methyl nicotinamide (MNA) and S-adenosylhomocysteine (SAH). NNMT has been shown to promote cell growth and proliferation in cancer cells.
563-	NO	↑	Nitric Oxide			Once the cancer has begun, NO seems to play a protumoral role rather than antitumoral one as the concentration required to cause tumor cell cytotoxicity cannot be achieved by cancer cells. The mechanistic roles of nitric oxide (NO) during cancer progression have been important considerations since its discovery as an endogenously generated free radical. Nonetheless, the impacts of this signaling molecule can be seemingly contradictory, being both pro-and antitumorigenic, which complicates the development of cancer treatments based on the modulation of NO fluxes in tumors. At a fundamental level, low levels of NO drive oncogenic pathways, immunosuppression, metastasis, and angiogenesis, while higher levels lead to apoptosis and reduced hypoxia and also sensitize tumors to conventional therapies. However, clinical outcome depends on the type and stage of the tumor as well as the tumor microenvironment. Nitric oxide is generated by three main nitric oxide synthase isoforms: neuronal (nNOS), endothelial (eNOS), and inducible (iNOS). – In many cancers, especially under inflammatory conditions, iNOS expression is upregulated. In contrast, eNOS levels may also be altered in cancers such as breast or prostate cancer. • Expression Patterns in Tumors: – Elevated iNOS expression is commonly observed in various tumor types (e.g., colon, breast, lung, and melanoma) and is often associated with an inflammatory microenvironment. – Changes in eNOS and nNOS expression have also been reported and may contribute to angiogenesis and tumor blood flow regulation.
409-	NOS2	↑	nitric oxide synthase 2			also known as NOS2A, INOS Nitric Oxide Synthase 2 (NOS2, also known as inducible NOS or iNOS) in cancer. elevated NOS2 has been shown to predict poor outcome in cancer such as ER- breast cancer, glioma, melanoma, cervical, liver, ovarian, and pancreatic. Taken together, NOS2 may be one of the most powerful biomarker and predictors of poor prognosis and an ideal target for cancer therapy. Many cancers exhibit upregulated NOS2 expression as part of the tumor-associated inflammatory response. – Examples include colorectal, breast, lung, and some head and neck cancers, where the inflammatory microenvironment can drive NOS2 induction.
220-	NOTCH	↑		HalifaxProj(block) CGL-CF TCGA		Notch signaling pathway is a regulator of self-renewal and differentiation in several tissues and cell types.; Notch hyperactivation has been implicated as oncogenic in several cancers including breast cancer and T-cell acute lymphoblastic leukemia (T-ALL). Due to its dual roles, NOTCH signaling is being explored as a therapeutic target. Inhibitors of NOTCH signaling are being investigated in clinical trials for various cancers, particularly those with aberrant NOTCH activation. The abnormal activation of the NOTCH pathway has been linked to increased cancer cell growth, survival, invasion, and resistance to chemotherapy and radiation therapy. On the other hand, blocking the NOTCH pathway has been shown to trigger cancer cell differentiation and cell death, and it makes them more responsive to therapy. Hence, inhibiting the NOTCH pathway has become a promising approach for treating cancer, and various NOTCH pathway inhibitors are currently under development for cancer treatment
221-	NOTCH1	⇅	Notch homolog 1, translocation-associated (Drosophila)	CGL-Driver Genes	TSG	NOTCH1 is a gene that encodes a protein involved in the Notch signaling pathway, which plays a crucial role in cell differentiation, proliferation, and apoptosis. Overall, the expression of NOTCH1 in cancer is complex and can have different implications depending on the tumor type and microenvironment. Notch1 is a transmembrane receptor involved in the Notch signaling pathway, a highly conserved mechanism that regulates cell differentiation, proliferation, and apoptosis. – Activation occurs following interaction with membrane-bound ligands (e.g., Jagged and Delta-like proteins) on adjacent cells, leading to proteolytic cleavage and release of the Notch intracellular domain (NICD). Notch1 expression can be upregulated or activated in many types of cancers, including T‑cell acute lymphoblastic leukemia (T‑ALL), breast cancer, and certain solid tumors. – In other contexts, such as in some squamous cell carcinomas and cancers of the colon, Notch1 signaling can be reduced, suggesting a dual role depending on the tissue of origin and tumor microenvironment.
222-	NOTCH2	⇅	Notch homolog 2 (Drosophila)	CGL-Driver Genes	TSG	NOTCH2 is a member of the Notch signaling pathway, which plays a crucial role in cell differentiation, proliferation, and apoptosis. NOTCH2 can act as either a tumor suppressor or an oncogene. Notch2 expression varies widely across cancer types. In some tumors, such as certain hematological malignancies and solid tumors like breast or lung cancer, Notch2 may be overexpressed or exhibit enhanced signaling activity. – In contrast, other studies have observed reduced expression of Notch2 in tumors like hepatocellular carcinoma or pancreatic cancer, suggesting that its role can differ based on tissue context and tumor subtype.
437-	NOTCH3	↑	Notch homolog 3			NOTCH3 is a member of the Notch signaling pathway, which plays a crucial role in cell communication, development, and differentiation. NOTCH3 can have both oncogenic (cancer-promoting) and tumor-suppressive roles, depending on the type of cancer and the cellular context. Overexpression in: breast, ovarian, lung, head and neck, gbm, pancreatic
1309-	NOX	↑	NADPH oxidase			NOX refers to the NADPH oxidase (NOX) family of enzymes, which generates reactive oxygen species (ROS) by transferring electrons from NADPH to molecular oxygen. Several NOX isoforms (e.g., NOX1, NOX2, NOX4, etc.) have been implicated in cancer biology. -NOX1 and NOX4 are frequently found to be upregulated in colorectal, prostate, and pancreatic cancers, while NOX2 is associated with cells in the tumor microenvironment (like macrophages).
644-	NOX4	↑	NADPH oxidase 4			NOX4 (NADPH oxidase 4) is a member of the NADPH oxidase (NOX) family of enzymes, which are responsible for generating reactive oxygen species (ROS) in various cell types. NOX4 is regulated by hypoxia, which can activate its expression and activity. NOX4 (NADPH oxidase 4) is an enzyme that produces reactive oxygen species (ROS), particularly hydrogen peroxide (H₂O₂). NOX4 is a cytoplasmic enzyme that catalyzes the transfer of electrons from NADPH to oxygen, resulting in the production of superoxide anion (O2-) and other ROS. NOX4 is expressed in a variety of tissues, including the kidney, lung, and vascular smooth muscle cells. NOX4 is generally expressed in cancer. In general, high NOX4 expression is associated with: Poor prognosis Increased tumor size Metastasis Resistance to chemotherapy and radiation therapy Poor response to treatment Low NOX4 expression is associated with: Better prognosis Smaller tumor size Less metastasis Better response to chemotherapy and radiation therapy Better response to treatment The combination of NOX4-driven ROS and available iron can lead to a synergistic increase in oxidative stress, setting the stage for ferroptotic cell death.
874-	NOXA	↓	Phorbol-12-myristate-13-acetate-induced protein 1 (PMAIP1)			NOXA is a pro-apoptotic protein that plays a crucial role in the regulation of apoptosis, or programmed cell death, in cancer cells. NOXA is a member of the BCL-2 family of proteins, which are key regulators of apoptosis. Low NOXA expression has been associated with poor prognosis and reduced overall survival
1050-	NPC1L1	⇅	Niemann–Pick C1-Like 1			NPC1L1 (Niemann–Pick C1-Like 1) is best known as a key mediator of intestinal cholesterol absorption and a target for cholesterol-lowering drugs (e.g., ezetimibe). Increasing evidence suggests that NPC1L1 may also play a role in cancer biology. Overall, NPC1L1 is emerging as a potential biomarker of altered lipid metabolism in cancer, and future studies may help clarify its utility as a prognostic indicator or therapeutic target.
223-	NPM1	↑	nucleophosmin 1 (nucleolar phosphoprotein B23, numatrin) pseudogene 21; hypothetical LOC100131044; similar to nucleophosmin 1; nucleophosmin (nucleolar phosphoprotein B23, numatrin)	CGL-Driver Genes	TSG	NPM1 (Nucleophosmin) is a gene that encodes a protein involved in various cellular processes, including ribosome biogenesis, cell proliferation, and stress response. Mutations in the NPM1 gene are particularly associated with acute myeloid leukemia (AML), a type of cancer that affects the blood and bone marrow. NPM1 is often overexpressed in various cancers, including breast cancer, lung cancer, and colorectal cancer. Strategies to inhibit its function or correct its mislocalization may offer new avenues for cancer treatment.
528-	NPY	⇅	Neuropeptide Y			NPY and Y2R are overexpressed in human Colon cancer, orthotopic HT29, and most interestingly in VEGF-A-depleted orthotopic HT29 tumours. NPY favors tumor cell growth, migration, and metastasis and promotes angiogenesis in some tumors (e.g., breast cancer, colorectal cancer, neuroblastoma, pancreatic cancer), whereas in others it exerts an antitumor effect (e.g., cholangiocarcinoma, Ewing sarcoma, liver cancer). Increased NPY signaling has been correlated with aggressive features in certain tumors, as it may promote cell proliferation, angiogenesis, and migration. – In cancers where NPY receptor expression is high, particularly the Y1 and Y2 receptors, the activation of NPY signaling cascades can correlate with poorer prognosis, tumor growth, or enhanced metastatic potential.
224-	NQO1	↑	NAD(P)H quinone dehydrogenase 1			NQO1 has attracted interest due to its roles in cell defense and marked inducibility during cellular stress. Since NQO1 is highly expressed in many solid tumors, including via upregulation of Nrf2, the design of compounds activated by NQO1 and NQO1-targeted drug delivery have been active areas of research. NQO1 (NAD(P)H:quinone oxidoreductase 1) is an enzyme that plays a significant role in cellular defense against oxidative stress and the metabolism of various compounds, including quinones and other electrophiles. Its function is crucial in protecting cells from damage caused by reactive oxygen species (ROS) and in the detoxification of potentially harmful substances.
435-	NQO2	?	N-ribosyldihydronicotinamide:quinone reductase 2			Curcumol exhibits synergistic lethal effects with TRAIL on cancer cell by directly targeting quinone oxidoreductase 2 (NQO2) to induce reactive oxygen species, triggering ER stress‐C/EBP homologous protein (CHOP)‐death receptor 5 (DR5) signaling to combat TRAIL‐resistant cancer.
225-	NRAS	↑	neuroblastoma RAS viral (v-ras) oncogene homolog	CGL-Driver Genes	Oncogene	NRAS (Neuroblastoma RAS viral oncogene homolog) is a gene that encodes a protein involved in cell signaling pathways that regulate cell growth and differentiation. When NRAS is mutated or overexpressed, it can lead to uncontrolled cell proliferation and contribute to tumorigenesis.
878-	Nrf1	⇅	Nuclear factor erythroid 2-related factor 1		transcription factor	Nrf1 (Nuclear factor erythroid 2-related factor 1) is a transcription factor that plays a crucial role in regulating cellular responses to stress, including oxidative stress and proteotoxic stress. While Nrf1 is generally considered a tumor suppressor, its expression and activity can be altered in various types of cancer, leading to either oncogenic or tumor-suppressive effects. NRF1, together with related factors like NRF2, contributes to the cellular defense against oxidative damage by regulating antioxidant gene expression. – This role can be double-edged: while it protects normal cells from damage, in cancer cells, enhanced antioxidant capacity might foster resistance to therapeutic agents that rely on oxidative stress to kill tumor cells.
226-	NRF2	↑	nuclear factor erythroid 2-related factor 2	TCGA	Antiapoptotic	Nrf2 is responsible for regulating an extensive panel of antioxidant enzymes involved in the detoxification and elimination of oxidative stress. 1. Raising Nrf2 enhances the cell's antioxidant defenses and ↓ROS. This strategy is used to decrease chemo-radio side effects. 2. Downregulating Nrf2 lowers antioxidant defenses and ↑ROS. In cancer cells this leads to DNA damage, and cell death. In some cases, Nrf2 is overexpressed in cancer cells, which can lead to the activation of genes involved in cell proliferation, angiogenesis, and metastasis. This can contribute to the development of resistance to chemotherapy and targeted therapies. Increased Nrf2 expression: Lung, Breast, Colorectal, Prostrate. Decreased Nrf2 expression: Skine, Liver, Pancreatic -Major regulator of Nrf2 activity in cells is the cytosolic inhibitor Keap1 https://biosignaling.biomedcentral.com/articles/10.1186/s12964-022-00906-3 Nrf2 inhibitors: Brusatol, Luteolin, Trigonelline, VitC, Retinoic acid, Chrysin Nrf2 Activators: SFN, OPZ EGCG, Resveratrol, DATS, CUR, CDDO, Api, SFN Nrf2 plays dual roles in that it can protect normal tissues against oxidative damage and can act as an oncogenic protein in tumor tissue – In healthy tissues, NRF2 activation helps protect cells from oxidative damage and maintains cellular homeostasis. – In many cancers, constitutive activation of NRF2 (often through mutations in NRF2 itself or loss-of-function mutations in KEAP1) leads to an enhanced antioxidant capacity. – This upregulation can promote tumor cell survival by enabling cancer cells to thrive under oxidative stress, resist chemotherapeutic agents, and sustain metabolic reprogramming. – Elevated NRF2 levels have been implicated in promoting tumor growth, metastasis, and resistance to therapy in various malignancies. – High or sustained NRF2 activity is frequently associated with aggressive tumor phenotypes, poorer prognosis, and decreased overall survival in several cancer types. - While its activation is essential for protecting normal cells from oxidative stress, aberrant or sustained NRF2 activation in tumor cells can lead to enhanced survival, therapeutic resistance, and tumor progression. NRF2 inhibitors: (to decrease antioxidant defenses and increase cell death from ROS) -Brusatol: most cited natural inhibitors of Nrf2. -Luteolin: luteolin can reduce Nrf2 activity in specific cancer models and may enhance cell sensitivity to chemotherapy. However, luteolin is also known as an antioxidant, and its influence on Nrf2 can sometimes be context dependent. -Apigenin: certain studies to down‑regulate Nrf2 in cancer cells: effect may vary with dose and context. -Oridonin: -Wogonin: it appears to suppress Nrf2‑mediated defense mechanisms, although its effects might be cell‑ and dose‑specific.
537-	NSE	↑	Neuron-specific enolase			NSE, (or gamma-enolase or enolase 2) is a cytosolic protein consistently expressed by mature neurons and cells of neuronal origin. NSE is commonly used as a marker for neurons and neuroendocrine cells, making it a useful tool for assessing neuronal injury and neuroendocrine tumors. Neuron-specific enolase (NSE) has become a widely used and easily attainable laboratory assay of small cell lung cancer (SCLC). Elevated serum NSE before any therapy of SCLC patients may be a negative prognostic factor for OS and PFS. The level of NSE correlates with tumour burden, number of metastatic sites and response to treatment.
228-	nucleolin	↑	nucleolin			In addition, nucleolin expressed at the cell surface binds a variety of ligands that have been implicated in tumorigenesis and angiogenesis. expression and localization of nucleolin is often abnormal in cancers. Meng et al6 indicated that a decrease of cell-surface nucleolin expression, or activity would inhibit the growth of cancer cells and trigger the apoptosis in endothelial cells. Dysregulated accumulation of nucleolin mRNA and protein is found in a diverse range of cancers, and the level of surface nucleolin in cancers is much higher than in normal cells.7 The elevated expression of nucleolin is associated with a worse prognosis of cancer patients, and the presence of nucleolin on the cell surface increases the malignancy of cancer and modulates the metastasis.
1148-	OAA	∅	oxaloacetate			OAA is not an enzyme or protein but a key metabolic intermediate. OAA plays a central role in multiple metabolic pathways, including the tricarboxylic acid (TCA) cycle and gluconeogenesis, rather than being “expressed” in the traditional sense. -OAA is an intermediate in the TCA cycle (citric acid cycle), which is crucial for energy production in cells. -It also serves as a substrate for gluconeogenesis (conversion into phosphoenolpyruvate by PEPCK) and amino acid biosynthesis. -Because of its central metabolic position, changes in OAA availability can affect the balance between oxidative phosphorylation and glycolysis—a balance that is often disrupted in cancer cells (the Warburg effect). -upregulation of pyruvate carboxylase (which converts pyruvate to OAA) has been associated with aggressive tumor behavior in certain cancers (e.g., lung and breast cancers). -Similarly, altered malate dehydrogenase activity, which interconverts malate and OAA, has also been linked to metabolic shifts in cancer cells that correlate with prognosis. -These associations are often interpreted as markers of metabolic reprogramming rather than direct “OAA expression.” -Altered activities of enzymes that govern OAA production or utilization are associated with aggressive tumor phenotypes, making them of interest both as potential prognostic biomarkers and as therapeutic targets.
1053-	OATPs	⇅	Organic Anion Transporting Polypeptides			• OATP1B1 and OATP1B3 are mainly liver-specific transporters normally responsible for hepatic drug and solute uptake. – Their downregulation in HCC is associated with a loss of normal liver function and may indicate poorer prognosis. • OATP1B3 is also found to be aberrantly overexpressed in certain extrahepatic cancers, raising interest as a potential diagnostic or therapeutic marker. • OATP2B1 is more broadly expressed and its dysregulation in cancers like colorectal and prostate cancer might impact tumor behavior and treatment response, although further studies are needed to validate its prognostic significance.
1062-	OATs	?	Organic Anion Transporters			OATs (Organic Anion Transporters) are a family of membrane transport proteins primarily involved in the uptake and disposition of organic anions, including drug metabolites, toxins, and endogenous compounds. They belong mainly to the SLC22 gene family. OATs are expressed in a variety of tissues—with high expression in the kidney, liver, and to some extent in the intestine and brain. • In cancers, the expression of OATs can be altered (either downregulated or, in some contexts, upregulated) relative to the corresponding normal tissue.
930-	Obesity	↑	Obesity
778-	OCN	↑	Osteocalcin		protein	OCN (Osteocalcin) is a protein that is primarily produced by osteoblasts and plays a crucial role in bone mineralization and calcium ion homeostasis. OCN is overexpressed in: breast, lung, osteosarcoma cancers.
846-	OCR	↓	Oxygen consumption rate			Oxygen consumption rate (OCR) is a measure of the rate at which cells consume oxygen, and it has been found to be altered in cancer cells. Cancer cells often exhibit increased glycolysis, a process in which glucose is converted into energy without the use of oxygen, even in the presence of oxygen. This is known as the Warburg effect. Cancer cells often exhibit increased glycolysis, which leads to a decrease in OCR.
508-	OCT4	↑	Octamer-binding transcription factor 4			POU5F1 is a gene that encodes a transcription factor also known as Oct4 OCT4 (Octamer-binding transcription factor 4) is a transcription factor that plays a crucial role in maintaining the pluripotency and self-renewal of embryonic stem cells. It is part of the core regulatory network that governs stem cell identity and is essential for the early stages of development. OCT4 is often expressed in cancer stem cells, which are a subpopulation of cells within tumors that possess the ability to self-renew and drive tumorigenesis. The presence of OCT4 in these cells is associated with increased tumor aggressiveness and resistance to conventional therapies.
791-	oncosis	?	oncosis		type of cell death	Oncosis is a type of cell death that is characterized by cell swelling, organelle swelling, and eventual rupture of the cell membrane. It is often referred to as "accidental cell death" or "necrotic cell death" because it is not a programmed or regulated process, unlike apoptosis (programmed cell death).
1184-	OPG	?	OPG			OPG production in breast cancer cells has been linked to differences in tumor behavior. Some studies suggest that higher OPG expression might counteract RANKL-mediated bone resorption, potentially reducing the risk of bone metastasis. Prognosis: -A protective effect has been proposed in certain contexts—elevated OPG levels might be associated with a lower incidence of bone metastasis. -In contrast, other reports indicate that high circulating OPG levels may correlate with a poorer overall prognosis. This discrepancy could be influenced by whether OPG is functioning in a paracrine fashion within the tumor microenvironment or as a systemic biomarker.
779-	OPN	↑	Osteopontin		protein	OPN (Osteopontin) is a protein that is involved in various cellular processes, including cell adhesion, migration, and survival. OPN is overexpressed in: breast, prostate, lung, ost, CRC, GC, Pancreatic, HCC, RCC, GBM, crevical, ovarian cancers.
229-	OS	?	overall survival
628-	OSI	?	oxidative stress index
589-	OSM	⇅	oncostatin			OSM is a protein that belongs to the interleukin-6 (IL-6) family of cytokines. OSM has been shown to have both tumor-promoting and tumor-suppressing effects, depending on the type of cancer and the context in which it is expressed. Tumor-promoting effects: Angiogenesis: OSM can stimulate the formation of new blood vessels, which is essential for tumor growth and metastasis. Cell proliferation: OSM can promote the proliferation of cancer cells, particularly in breast, lung, and colon cancers. Inflammation: OSM can induce the production of pro-inflammatory cytokines, which can create a tumor-friendly microenvironment. Tumor-suppressing effects: Apoptosis: OSM can induce apoptosis (programmed cell death) in certain types of cancer cells, such as melanoma and leukemia. Anti-angiogenesis: OSM can also inhibit the formation of new blood vessels, which can limit tumor growth. Immune response: OSM can stimulate the immune system to attack cancer cells, particularly in the context of immunotherapy.
767-	other	?	other			custom
819-	OV6	↑	OV6			OV6 is a monoclonal antibody that recognizes a specific antigen expressed on the surface of certain cancer cells, particularly those of epithelial origin. The OV6 antigen is a glycoprotein that is overexpressed on the surface of many types of cancer cells. OV6+ refers to a specific subset of cells that express the OV6 antigen. In other words, OV6+ cells are cells that have been identified as expressing the OV6 antigen, typically using the OV6 antibody.
230-	OXPHOS	↑	Oxidative phosphorylation			Oxidative phosphorylation (or phosphorylation) is the fourth and final step in cellular respiration. Alterations in phosphorylation pathways result in serious outcomes in cancer. Many signalling pathways including Tyrosine kinase, MAP kinase, Cadherin-catenin complex, Cyclin-dependent kinase etc. are major players of the cell cycle and deregulation in their phosphorylation-dephosphorylation cascade has been shown to be manifested in the form of various types of cancers. Many tumors exhibit a well-known metabolic shift known as the Warburg effect, where glycolysis is favored over OxPhos even in the presence of oxygen. However, this is not universal. Many cancers, including certain subpopulations like cancer stem cells, still rely on OXPHOS for energy production, biosynthesis, and survival. – In several cancers, especially during metastasis or in tumors with high metabolic plasticity, OxPhos can remain active or even be upregulated to meet energy demands In some cancers, high OxPhos activity correlates with aggressive features, resistance to standard therapies, and poor outcomes, particularly when tumor cells exploit mitochondrial metabolism for survival and metastasis. – Conversely, low OxPhos activity can be associated with a reliance on glycolysis, which is also linked with rapid tumor growth and certain adverse prognostic features Inhibiting oxidative phosphorylation is not a universal strategy against all cancers. Targeting OXPHOS can potentially disrupt the metabolic flexibility of cancer cells, leading to their death or making them more susceptible to other treatments. Since normal cells also rely on OXPHOS, inhibitors must be carefully targeted to avoid significant toxicity to healthy tissues. Not all tumors are the same. Some may be more glycolytic, while others depend more on mitochondrial metabolism. Therefore, metabolic profiling of tumors is crucial before adopting this strategy. Inhibiting OXPHOS is being explored in combination with other treatments (such as chemo- or immunotherapies) to improve efficacy and overcome resistance. In cancer cells, metabolic reprogramming is a hallmark where cells often rely on glycolysis (known as the Warburg effect); however, many cancer types also depend on OXPHOS for energy production and survival. Targeting OXPHOS(using inhibitor) to increase the production of reactive oxygen species (ROS) can selectively induce oxidative stress and cell death in cancer cells. -One side effect of increased OXPHOS is the production of reactive oxygen species (ROS). -Many cancer cells therefore simultaneously upregulate antioxidant systems to mitigate the damaging effects of elevated ROS -increase in oxidative phosphorylation can inhibit cancer growth
232-	P-gp	↑	permeability-glycoprotein			P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1), is a membrane protein that plays a crucial role in the transport of various substances across cellular membranes. It is part of the ATP-binding cassette (ABC) transporter family. P-glycoprotein is often overexpressed in a variety of cancers, including breast cancer, lung cancer, leukemia, and ovarian cancer. - The overexpression of P-glycoprotein (P-gp), is widely considered as an important reason for the MDR (multidrug resistance)
727-	p16	↓	protein 16		tumor suppressor protein	p16 is a protein that plays a crucial role in regulating the cell cycle and preventing cancer. It is a tumor suppressor protein that helps to prevent the uncontrolled growth of cells. p16 is a cyclin-dependent kinase inhibitor, which means that it helps to regulate the activity of certain enzymes (cyclin-dependent kinases) that drive the cell cycle forward. By inhibiting these enzymes, p16 helps to slow down or stop the cell cycle, giving the cell time to repair any DNA damage that may have occurred. p16 has been shown to be inactivated in many types of cancer, including breast, lung, and colon cancer.
909-	p19	↓	p19/CDKN2D			p19, also known as CDKN2D, is a tumor suppressor protein that plays a crucial role in regulating cell cycle progression and preventing cancer. In cancer, p19 is often downregulated or mutated, leading to uncontrolled cell growth and tumor development.
234-	P21	↓			Proapototic	cyclin-dependent kinase inhibitor p21 (also known as p21 WAF1/Cip1) promotes cell cycle arrest in response to many stimuli. P21 is a cyclin-dependent kinase inhibitor that plays a crucial role in regulating the cell cycle. It is encoded by the CDKN1A gene and is a key player in the cellular response to stress, including DNA damage. P21 is often considered a tumor suppressor because its expression is upregulated in response to p53 activation, a well-known tumor suppressor protein. When DNA damage occurs, p53 can activate the transcription of the CDKN1A gene, leading to increased levels of P21, which helps prevent the proliferation of damaged cells. In many cancers, the p53 pathway is disrupted, leading to decreased levels of P21. p21 is a apoptotic marker protein. cell cycle arrest gene p21
468-	p27	↓	p27kip1			The cyclin-dependent kinase (Cdk) inhibitor p27 regulates cell proliferation, cell motility and apoptosis, and is inactivated through various means in many types of human cancer.
995-	P2X7	↑	purinoceptor 7			Purinoceptor 7 (commonly referred to as P2X7 when discussing purinergic receptors, though note that P2X7 is an ATP-gated ion channel; if referring to a distinct purinoceptor termed “purinoceptor 7” – Purinergic receptors are activated by extracellular nucleotides (e.g., ATP). In the context of P2X7, it is an ATP-gated ion channel that opens upon binding high concentrations of ATP. – This receptor’s activation allows the flow of ions (such as Ca²⁺, Na⁺, and K⁺) across the plasma membrane, thereby initiating intracellular signaling cascades. Cell Death and Proliferation: – Prolonged or high-level activation of P2X7 can induce a form of programmed cell death (apoptosis or pyroptosis) by forming membrane pores. – Conversely, under controlled conditions, P2X7 activation may promote cell proliferation and survival by triggering downstream signaling pathways responsible for growth and differentiation. – Elevated expression of P2X7 has been documented in several cancer types, including breast, prostate, colorectal, and hematologic malignancies. – Upregulation in tumor cells may occur either as an adaptive mechanism to the high extracellular ATP levels often found in the tumor microenvironment or as part of oncogenic signaling pathways. – In several studies, high P2X7 expression has been correlated with aggressive tumor behavior, metastasis, and reduced overall survival. Dual-Edge Effects: – In certain circumstances, activation of P2X7 leading to cell death may actually have antitumor effects.
901-	p300	↑	p300			p300 is a transcriptional coactivator protein that plays a crucial role in regulating gene expression, cell growth, and differentiation. p300 has been shown to promote tumor initiation and progression by regulating the expression of genes involved in cell growth, survival, and metastasis. p300 is overexpressed in various types of cancer, with poor prognosis.
235-	p38	↑	p38			P38, or p38 MAPK (p38 mitogen-activated protein kinase), is a protein kinase that plays a significant role in cellular responses to stress, inflammation, and apoptosis (programmed cell death). It is part of the MAPK signaling pathway, which is involved in various cellular processes, including cell growth, differentiation, and survival. It can have both tumor-suppressive and tumor-promoting effects, depending on the type of cancer and the cellular context. -p38 activation can contribute to tumor progression by influencing inflammatory signaling and cell-cycle regulation. -Overexpression can correlate with poor prognosis in some studies.
481-	p42	↑	p42 MAPK			The p42 protein often refers to a specific isoform of the mitogen-activated protein kinase (MAPK) pathway, particularly p42 MAPK, which is also known as extracellular signal-regulated kinase 2 (ERK2). This protein plays a crucial role in various cellular processes, including proliferation, differentiation, and survival. The activation of p42 MAPK has been associated with various types of cancer, including melanoma, breast cancer, and colorectal cancer. p42—which is commonly used to refer to the ~42 kDa isoform of extracellular signal‑regulated kinases (ERK), often designated as ERK2 (p42 MAPK)—in cancer. This summary covers its expression trends, prognostic implications, and functional roles in tumor biology. Note that the MAPK/ERK pathway is complex and highly context‑dependent, with ERK2 (p42) frequently working in concert with its counterpart ERK1 (p44) to regulate diverse cellular processes. In many cancers, the MAPK/ERK pathway is hyperactivated due to upstream mutations (e.g., in RAS or BRAF), leading to increased levels of active (phosphorylated) p42. – While the total expression of ERK2 may be relatively stable, the activated/phosphorylated form is frequently elevated, reflecting increased signaling activity. – This activation is observed in a variety of cancers including melanoma, colorectal cancer, lung cancer, and thyroid cancer p42 is not exactly the same as "ERK" in general but is closely related. In many contexts, p42 refers specifically to the 42‑kDa isoform of the extracellular signal-regulated kinases (ERKs), often known as ERK2. Typically, cells express two closely related isoforms of ERK: one is about 44 kDa (ERK1, sometimes called p44) and the other is about 42 kDa (ERK2, or p42). Both of these are members of the mitogen-activated protein kinase (MAPK) family and play key roles in cellular signaling. So, when someone refers to p42 in the context of MAPK signaling, they are usually talking about ERK2, whereas "ERK" can be used to refer to both isoforms (ERK1 and ERK2) collectively.
482-	p44	↑	p44/ERK1			The P44 protein, also known as p44 or p44/ERK1, is a member of the mitogen-activated protein kinase (MAPK) family, specifically the extracellular signal-regulated kinases (ERKs). These proteins play a crucial role in various cellular processes, including proliferation, differentiation, and survival, and are involved in signaling pathways that can influence cancer development and progression p44 tends to be overexpressed in several hormone–driven and other cancers, correlating with more aggressive disease and poorer prognosis, thereby acting in a protumorigenic manner.
1061-	P450	↑	cytochrome P450 (CYP) family			The cytochrome P450 (CYP) family includes many isoenzymes that play key roles in metabolizing endogenous substances (like hormones) and xenobiotics (including drugs and toxins). Changes in the expression of these enzymes in various cancers can affect carcinogen activation, drug metabolism, and overall tumor biology, influencing both cancer risk and prognosis. CYP1B1 – Frequently overexpressed in several cancers including breast, ovarian, prostate, and colorectal cancers. – Its expression is often low in normal tissues, making it a potential target for selective cancer therapies. 2. CYP3A4 and CYP3A5 These enzymes are highly expressed in the liver, but their expression is also observed in extrahepatic tissues. – In cancer, CYP3A enzymes can be variably expressed; for instance, CYP3A4 may be upregulated in some liver cancers but downregulated in others. 3. CYP2E1 – CYP2E1 is expressed in the liver and extrahepatic tissues. – Elevated CYP2E1 activity can lead to increased production of reactive oxygen species (ROS), contributing to DNA damage and cancer progression. 4. CYP19A1 (Aromatase) – Aromatase converts androgens to estrogens and is expressed in adipose tissue as well as in certain tumors such as breast cancer. – Its local expression in breast tumors can increase estrogen levels, promoting hormone-dependent tumor growth. 5. CYP2C Family (e.g., CYP2C8, CYP2C9, CYP2C19) – These enzymes are involved in metabolizing various drugs and are expressed in the liver and intestines. – Their expression levels can be altered in different tumor types, potentially affecting drug metabolism. CYP450 enzymes are a large family with diverse roles in cancer biology. • Their expression in cancers (e.g., CYP1B1, CYP3A4/5, CYP2E1, CYP19A1) has been linked to both the development and progression of tumors, as well as influencing responses to therapy.
842-	p50	↑	p50			p50 is a protein that is part of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factor complex. NF-κB is a key regulator of immune responses, inflammation, and cell survival, and it plays a critical role in the development and progression of various types of cancer. p50 is one of the two subunits of the NF-κB complex, the other being p65. The p50/p65 heterodimer is the most common form of NF-κB, and it is activated by a wide range of stimuli, including cytokines, growth factors, and stress. In cancer, p50 is often overexpressed or constitutively activated, leading to the promotion of cell proliferation, survival, and metastasis.
236-	P53	↑	P53-Guardian of the Genome	TCGA	Proapototic	TP53 is the most commonly mutated gene in human cancer. TP53 is a gene that encodes for the p53 tumor suppressor protein ; TP73 (Chr.1p36.33) and TP63 (Chr.3q28) genes that encode transcription factors p73 and p63, respectively, are TP53 homologous structures. p53 is a crucial tumor suppressor protein that plays a significant role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress. TP53 gene, which encodes the p53 protein, is one of the most frequently mutated genes in human cancers. overexpression of MDM2, an inhibitor of p53, can lead to decreased p53 activity even in the presence of wild-type p53. In some cancers, particularly those with mutant p53, there may be an overexpression of the p53 protein. Cancers with overexpression: Breast, lung, colorectal, overian, head and neck, Esophageal, bladder, pancreatic, and liver.
237-	p53 Wildtype	↓		HalifaxProj(upregulate)		The term "wildtype" refers to the normal, non-mutated form of the p53 protein. In this state, p53 is functional and can effectively carry out its tumor-suppressing activities. Wildtype p53 can induce cell cycle arrest, promote DNA repair, initiate apoptosis (programmed cell death), and regulate other genes involved in these processes. It responds to various stress signals, such as DNA damage, hypoxia, and oncogene activation. In Cancers with Wild-Type p53: Intact p53 function is associated with better control of cell growth and an improved response to DNA damage. Retention of wild-type p53 generally indicates a more favorable prognosis. Wild-Type p53: Classic tumor-suppressing role (i.e., anti-tumorigenic). It prevents the proliferation of cells with damaged DNA. Mutant p53: Can be considered protumorigenic due to loss of normal function and, in certain cases, due to “gain-of-function” activities.
602-	p62	↑	p62/sequestosome 1 (SQSTM1)			a protein that plays a crucial role in various cellular processes, including autophagy, cell signaling, and protein degradation. p62 is a scaffold protein that interacts with various signaling molecules, including kinases, phosphatases, and ubiquitin ligases. It is also a substrate of autophagy, a process by which cells recycle damaged or dysfunctional organelles and proteins. p62 is overexpressed in various types of cancer, including breast, lung, colon, and liver cancer. Its overexpression has been associated with poor prognosis and reduced survival in some cancers.
238-	p65	↑	RelA			P65, also known as RelA, is a subunit of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) transcription factor complex. NF-κB plays a crucial role in regulating immune response, inflammation, and cell survival. Due to its role in cancer progression, p65 and the NF-κB pathway are considered potential therapeutic targets. Inhibitors of NF-κB signaling are being explored in preclinical and clinical studies as potential cancer treatments. Many studies have reported that p65 is overexpressed in various types of cancers, including breast, prostate, lung, and colorectal cancers. In some cancers, elevated p65 levels correlate with higher grades of tumors and advanced stages of disease. "RELA proto-oncogene, NF-κB subunit." It encodes the p65 protein, which is a central component of the NF‑κB transcription factor complex. -Chronic activation of RELA and the NF‑κB pathway is frequently associated with cancer progression, promoting inflammation-driven tumorigenesis, chemoresistance, and metastasis. -RELA interacts with other oncogenic signaling networks (for example, STAT3 and MAPK pathways), further integrating environmental signals that favor cancer progression. RELA (p65) is a critical subunit of the NF‑κB transcription factor complex, involved in the regulation of genes that control inflammation, cell survival, and proliferation. In the context of cancer, aberrant activation and overexpression of RELA are frequently associated with aggressive tumor behavior, therapy resistance, and poorer patient outcomes in cancers such as breast, lung, colorectal, and pancreatic cancers, among others. RELA emerges as a potential key contributor to the suppression of glycolysis, mitochondrial respiration, and ATP production in cancer cells. (RELA knockdown signifcantly reduced the tumorigenic potential of various pancreatic cancer cell lines)
1215-	p66Shc	⇅	p66Shc			p66Shc is one of three isoforms encoded by the ShcA gene and is well known for its roles in oxidative stress response, apoptosis, and cellular metabolism. • Some studies have revealed that altered p66Shc expression is associated with changes in oxidative stress signaling. • Elevated p66Shc activity in certain contexts has been linked to enhanced reactive oxygen species (ROS) production, which may promote tumor progression. • However, the exact relationship is complex; in some research, higher p66Shc levels have been associated with increased cancer cell apoptosis and a better prognosis, while in other studies a pro-oxidative environment may favor tumor aggressiveness.
733-	p70S6	↑	phospho-S6			p70S6, also known as phospho-S6, is the phosphorylated form of the S6 protein, which is a component of the 40S ribosomal subunit. The S6 protein is a key regulator of protein synthesis, and its phosphorylation by p70S6K is a critical event in the regulation of translation. Overexpresed in: breast, prostate, lung CRC pancreatic, ovarian, Melanoma, HCC, RCC, throid, Esophageal, stomach.
488-	P70S6K	↑	p70 S6 kinase			P70S6K, or p70 S6 kinase, is a protein kinase that plays a significant role in the signaling pathways related to cell growth, proliferation, and survival. It is part of the mTOR (mechanistic target of rapamycin) signaling pathway, which is crucial for regulating cellular metabolism and growth in response to nutrients, growth factors, and stress signals. Expression Direction: In many cancers, p70S6K is frequently found to be overexpressed or hyperactivated. Increased phosphorylation (activation) of p70S6K is often detected, correlating with enhanced mTOR signaling. Elevated levels or hyperactivation of p70S6K in tumor tissues are generally associated with: More aggressive tumor behavior and higher proliferative indices. A poorer prognosis in several cancer types. • In cancers such as breast, lung, and gastrointestinal cancers, high p70S6K activity may correlate with advanced disease and decreased overall survival.
750-	p73	↓	p73		protein	p73 is a protein that plays a crucial role in regulating cell growth, differentiation, and death. It is a member of the p53 family of proteins, which are known as tumor suppressors. p73 is often inactivated or downregulated in various types of cancer, including breast, lung, and brain cancer.
1071-	p85S6K	↑	isoform of S6 kinase			S6 kinases are a family of serine/threonine kinases that play an important role in mediating protein synthesis, cell growth, and metabolism. They are downstream effectors of the mTOR pathway, a central regulator of cellular metabolism that integrates signals from nutrients, growth factors, and energy status. • p85 S6K Specifics: The p85 S6K isoform (sometimes noted in contrast to other S6K isoforms such as p70 S6K) has been identified in certain cell types and under specific conditions. While the p70 isoform is more widely studied, p85 S6K has been associated with distinct regulatory roles, potentially linking mTOR signaling with other cellular processes. Overactivation of mTOR and its downstream targets (including S6K) frequently correlates with enhanced cell growth, survival, and metabolic reprogramming in tumor cells. Increased S6K activity (and by extension, higher levels of p85 S6K in relevant contexts) has sometimes been correlated with poor prognosis, including lower overall survival and increased tumor aggressiveness. The p85 S6K isoform, as part of the broader mTOR/S6K axis, plays a role in regulating protein synthesis and cell proliferation—a link that is particularly significant in cancer. Its expression and activation status have been associated with tumor aggressiveness and poor prognosis in certain cancers
1134-	P90RSK	↑	90 kDa Ribosomal S6 Kinase			p90RSK (90 kDa Ribosomal S6 Kinase) p90RSK is a serine/threonine kinase and a downstream effector of the MAPK/ERK signaling pathway. It plays a critical role in regulating cellular processes such as proliferation, survival, migration, and protein synthesis, all of which can contribute to tumor development and progression. – p90RSK is activated in response to mitogenic stimuli through the MAPK/ERK pathway. – Once activated, it phosphorylates a variety of substrates that promote cell cycle progression and proliferation. – Aberrant activation of p90RSK may lead to uncontrolled cell division, a hallmark of cancer. – Several studies have reported that elevated p90RSK activity or expression is found in various tumor types, including breast, lung, and prostate cancers. – High levels of activated p90RSK are often associated with aggressive tumor behavior, enhanced proliferation, and metastatic potential.
576-	Pain	?	Pain
363-	PAK	↑	p21-activated kinases			Pak function is increased in many human cancers PAK family members (e.g., PAK1, PAK2, PAK3, PAK4, PAK5/7, etc.) and their roles may vary by cancer type, cellular context, and tumor stage. Much of the literature focuses on PAK1 and PAK4, which are most frequently associated with protumorigenic functions.
240-	PAK1	↑				PAK1 (p21-activated kinase 1) is a serine/threonine kinase that plays a significant role in various cellular processes, including cell motility, proliferation, and survival. PAK1 is often found to be overexpressed in several types of cancers, including breast cancer, prostate cancer, colorectal cancer, and pancreatic cancer. PAK1 expression can be regulated by various oncogenic signaling pathways, including those involving RAS, PI3K/Akt, and MAPK. These pathways can lead to the activation of PAK1, further promoting cancer cell survival and proliferation. In many cancer types, PAK1 expression and/or activity is frequently upregulated. Overexpression and/or hyperactivation of PAK1 has been reported in breast, ovarian, colorectal, lung, and other cancers
664-	PAO	↑	PAO gene			The PAO gene, also known as the polyamine oxidase gene, is a gene that encodes for the enzyme polyamine oxidase. This enzyme is involved in the breakdown of polyamines, which are small molecules that play a crucial role in various cellular processes, including cell growth, differentiation, and survival. The PAO gene is located on chromosome 10q23 in humans and is composed of 10 exons. The gene is highly conserved across different species, suggesting its importance in maintaining cellular homeostasis. Overexpressed: Breast, Lung, Colon Underexpressed: Prostate, Ovarian PAO (Polyamine Oxidase) catalyzes the oxidation of polyamines (e.g., N^1-acetylspermine) leading to products including H₂O₂, which is an ROS capable of promoting DNA damage. PAO inhibitors are being studied for their potential to modulate oxidative stress and affect polyamine balances in tumors, although this work is still largely in the early stages. In summary, while the PAO gene product—polyamine oxidase—is generally reported to be upregulated or more active in several tumor types (such as prostate, colorectal, and some breast cancers) and is associated with mechanisms that may promote tumor progression (for example, by generating oxidative stress), the literature is still evolving.
1246-	PAR-2	↑	Protease-activated receptor 2			Protease-activated receptor 2 (PAR-2), a member of the G protein-coupled receptor family, is activated by proteolytic cleavage -elevated PAR-2 expression and activation in various cancers—including breast, colorectal, pancreatic, prostate, and others—are frequently associated with enhanced tumor invasiveness, a pro-inflammatory microenvironment, and poorer patient outcomes.
1078-	Paraptosis	↓	Paraptosis		type of cell death	Paraptosis is a form of programmed cell death that differs morphologically from apoptosis. – Key features include pronounced cytoplasmic vacuolation, mitochondrial and/or endoplasmic reticulum (ER) swelling, and the absence of classical apoptotic markers (such as caspase activation, DNA fragmentation, and membrane blebbing). – It is considered a caspase-independent cell death mechanism.
1240-	PARK2	↓	PARKIN			PARKIN (also known as PARK2) is an E3 ubiquitin ligase that plays a crucial role in mitochondrial quality control, cell cycle regulation, and apoptosis. Although PARKIN is best known for its involvement in Parkinson’s disease, an increasing number of studies have investigated its role in cancer. -PARKIN is recruited to damaged mitochondria, which are often sources of elevated ROS due to impaired electron transport chains. -By targeting dysfunctional mitochondria for autophagic degradation (mitophagy), PARKIN helps to mitigate excessive ROS production, preserving cellular redox balance. -reduced PARKIN expression generally correlates with more aggressive disease and worse prognosis in various cancers, including breast, lung, colorectal, liver, and pancreatic cancers.
239-	PARP	↑	poly ADP-ribose polymerase (PARP) cleavage			poly (ADP-ribose) polymerase (PARP) cleavage is a hallmark of caspase activation. PARP (Poly (ADP-ribose) polymerase) is a family of proteins involved in a variety of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP enzymes play a crucial role in repairing single-strand breaks in DNA. PARP has gained significant attention, particularly in the treatment of certain types of tumors, such as those with BRCA1 or BRCA2 mutations. These mutations impair the cell's ability to repair double-strand breaks in DNA through homologous recombination. Cancer cells with these mutations can become reliant on PARP for survival, making them particularly sensitive to PARP inhibitors. PARP inhibitors, such as olaparib, rucaparib, and niraparib, have been developed as targeted therapies for cancers associated with BRCA mutations PARP Family: The poly (ADP-ribose) polymerases (PARPs) are a family of enzymes involved in a number of cellular processes, including DNA repair, genomic stability, and programmed cell death. PARP1 is the predominant family member responsible for detecting DNA strand breaks and initiating repair processes, especially through base excision repair (BER). PARP1 Overexpression: In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported. High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage). Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.
400-	PARP1	↑	Poly [ADP-ribose] polymerase 1			PARP1 accounts for 90% of the PARP family of enzymes. PARP-1 (poly(ADP-ribose)-polymerase 1), mainly known for its protective role in DNA repair, also regulates inflammatory processes. The close connection between PARP1 and the tumor suppressor protein p53 is also of great interest to those who study the complex role of PARP1 in cancer promotion or suppression. PARP1 inhibition, which blocks the JNK-PARP1-JNK loop and ERK-mediated anti-apoptotic protein expression, will result in cancer apoptosis. PARP1 Overexpression: In several cancer types—including breast, ovarian, prostate, and lung cancers—elevated PARP1 expression and/or activity has been reported. High PARP1 expression in certain cancers has been associated with aggressive tumor behavior and resistance to therapies (especially those that induce DNA damage). Increased PARP1 activity may correlate with poorer overall survival in tumors that rely on DNA repair for survival.
1124-	pax	↑	paxillin			Paxillin is a multi-domain adaptor protein localized to focal adhesions that plays a critical role in integrin‐mediated signal transduction, cytoskeletal reorganization, and cellular motility. Not only the overall expression levels, but also the phosphorylation state of paxillin (e.g., at tyrosine residues) is crucial. Abnormal phosphorylation can alter its interactions and downstream signaling, further enhancing cancer cell motility and survival. paxillin is frequently upregulated or aberrantly activated in various cancers. High expression and/or abnormal phosphorylation status of paxillin tends to correlate with increased tumor aggressiveness, enhanced metastatic potential, and generally poorer prognosis.
241-	PAX5	↓	paired box 5	CGL-Driver Genes	TSG	PAX5 (Paired Box 5) is a transcription factor that plays a crucial role in the development of B cells, which are a type of white blood cell involved in the immune response. It is primarily expressed in B-lineage cells and is essential for B cell differentiation and function. PAX5 mutations can lead to the loss of function of the protein, which may result in the inability of B cells to properly differentiate. This can create an environment conducive to the development of leukemia or lymphoma. PAX5, as a key transcription factor in B-cell development, plays a critical role in the pathogenesis of B-cell malignancies. Its alteration—commonly observed as mutations, deletions, or fusion events—can impair normal differentiation and contribute to oncogenesis. In this setting, normal PAX5 function is tumor suppressive, and its disruption generally correlates with a more aggressive disease and poorer prognosis.
242-	PBRM1	↓	polybromo 1	CGL-Driver Genes	TSG	PBRM1 (Polybromo 1) is a gene that encodes a protein involved in chromatin remodeling and regulation of gene expression. It is part of the PBAF (Polybromo-associated BAF) complex, which plays a crucial role in various cellular processes, including cell cycle regulation, differentiation, and response to DNA damage. Mutations or alterations in the PBRM1 gene have been associated with several types of cancer, particularly renal cell carcinoma (RCC). In many cases, reduced expression or functional loss is the dominant pattern rather than overexpression.
888-	PCAF	↑	p300/CBP-associated factor			PCAF (p300/CBP-associated factor) is a histone acetyltransferase (HAT) that plays a crucial role in the regulation of gene expression.
866-	PCBP1	↑	Poly(rC) Binding Protein 1			PCBP1 (Poly(rC) Binding Protein 1) is a protein that plays a crucial role in the regulation of gene expression, particularly in the context of cancer. PCBP1 has been shown to promote tumor growth, invasion, and metastasis by regulating the expression of genes involved in cell proliferation, survival, and migration. PCBP1 has been found to be highly expressed in cancer stem cells, which are thought to be responsible for cancer initiation, progression, and recurrence.
552-	PCK1	⇅	phosphoenolpyruvate carboxykinase 1			Compelling evidence suggests that PCK1 is strongly expressed in CRC cells and that PCK1 promotes cancer cell proliferation by increasing the anabolic utilization of glucose and glutamine. The expression of PCK1 in cancer is tissue-specific. PCK1’s expression and role in cancer are complex and vary by tissue type and tumor microenvironment. In cancers such as hepatocellular carcinoma, PCK1 is often downregulated and this reduction is associated with poorer prognosis and a more aggressive tumor phenotype, suggesting a tumor-suppressive role. In other cancers such as colorectal, lung, or breast cancer, findings are mixed and depend on the metabolic context, with some evidence pointing to altered PCK1 levels contributing to metabolic reprogramming that supports tumor growth.
729-	PCLAF	↑	Proliferating Cell Nuclear Antigen-Associated Factor		protein, transcriptional coactivator	PCLAF (Proliferating Cell Nuclear Antigen-Associated Factor) is a protein that has been associated with cancer. It is a transcriptional coactivator that plays a role in the regulation of cell proliferation and DNA replication. Research has shown that PCLAF is overexpressed in various types of cancer, including breast, lung, and colon cancer. This overexpression has been linked to increased cell proliferation, tumor growth, and poor prognosis.
489-	PCNA	↑	Proliferating Cell Nuclear Antigen			Proliferating Cell Nuclear Antigen (PCNA) is a protein that plays a crucial role in DNA replication and repair. It acts as a processivity factor for DNA polymerase, helping to increase the efficiency of DNA synthesis. PCNA is also involved in various cellular processes, including cell cycle regulation, DNA damage response, and chromatin remodeling. PCNA is often overexpressed in many types of tumors. This overexpression is associated with increased cell proliferation, which is a hallmark of cancer. The elevated levels of PCNA can serve as a biomarker for tumor growth and progression.
709-	PD-1	↑	Programmed Death-1		protein	PD-1 (Programmed Death-1) is a protein that plays a crucial role in the immune system's ability to fight cancer. It is a checkpoint protein that helps regulate the immune response by preventing the immune system from attacking healthy cells. PD-1 is often exploited by cancer cells to evade the immune system. Cancer cells can produce proteins that bind to PD-1, inhibiting the immune response and allowing the cancer cells to grow and proliferate unchecked. However, researchers have discovered that blocking the PD-1 pathway can help restore the immune system's ability to fight cancer. This has led to the development of PD-1 inhibitors, a class of cancer therapies that target the PD-1 protein. PD-1: Upregulated on tumor-infiltrating lymphocytes (TILs), reflecting chronic antigen exposure and an “exhausted” T cell phenotype. PD-L1 and PD-L2: Frequently overexpressed by many tumor types (e.g., non–small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancers)
243-	PD-L1	↑	Programmed Death-Ligand 1			PD-L1 is a protein that plays a crucial role in the regulation of the immune system. PD-L1 helps to prevent the immune system from attacking healthy cells by binding to its receptor, PD-1, on immune cells. However, some cancer cells can exploit this mechanism by expressing high levels of PD-L1, which can help them evade immune detection. PD-L1 has become a key target for cancer immunotherapy, particularly in the development of checkpoint inhibitors. PD-1: Upregulated on tumor-infiltrating lymphocytes (TILs), reflecting chronic antigen exposure and an “exhausted” T cell phenotype. PD-L1 and PD-L2: Frequently overexpressed by many tumor types (e.g., non–small cell lung cancer, melanoma, renal cell carcinoma, head and neck cancers
706-	PD-L2	↑	Programmed Death-Ligand 2		protein	PD-L2 is a protein that plays a crucial role in the regulation of the immune system, particularly in the context of cancer. It is a ligand for the PD-1 (Programmed Death-1) receptor, which is expressed on the surface of T cells. PD-L2 is often overexpressed on the surface of tumor cells, where it can interact with PD-1 on T cells. This interaction can lead to the inhibition of T cell activation and proliferation, allowing the tumor cells to evade immune surveillance and continue to grow and proliferate.
333-	PDCD4	↓				PDCD4 (Programmed Cell Death 4) is a protein that has been studied for its role in cancer biology. It is known to function as a tumor suppressor, meaning it helps prevent the formation and growth of tumors. PDCD4 is involved in various cellular processes, including apoptosis (programmed cell death), cell proliferation, and the regulation of gene expression. In many cancer types (such as lung, breast, colorectal, and ovarian cancers), PDCD4 expression is decreased relative to normal tissues. – Loss or reduced expression of PDCD4 is frequently observed at the mRNA and protein levels in tumor samples
361-	PDGF	↑	Platelet-derived growth factors			Activation of the PDGF/PDGFR signaling pathway is associated with cancer proliferation, metastasis, invasion, and angiogenesis Many tumor types exhibit increased PDGF ligand and/or receptor expression, leading to autocrine or paracrine stimulation of cancer cells as well as the surrounding stromal cells. – High PDGF signaling is noted in gliomas, sarcomas, breast cancer, and other solid tumors, where it contributes to tumor growth and angiogenesis.
826-	PDGFR-BB	↑	Platelet-Derived Growth Factor Receptor Beta Beta			PDGFR-BB (Platelet-Derived Growth Factor Receptor Beta Beta) is a protein that plays a crucial role in cell growth and division. PDGFR-BB has been implicated in the development and progression of various types of tumors, including glioblastoma, breast cancer, lung cancer, and others. Overexpression or mutation of PDGFR-BB can lead to uncontrolled cell proliferation, angiogenesis, and metastasis
244-	PDGFRA	↑	platelet-derived growth factor receptor, alpha polypeptide	CGL-Driver Genes	Oncogene	PDGFRA (Platelet-Derived Growth Factor Receptor Alpha) is a receptor tyrosine kinase that plays a significant role in cell growth, survival, and differentiation. It is part of the PDGF family, which includes various growth factors that bind to PDGF receptors to regulate cellular functions. Cancers, such as gastrointestinal stromal tumors (GISTs), are often associated with mutations in the PDGFRA gene. Imatinib (Gleevec) is a tyrosine kinase inhibitor that is effective in treating GISTs with PDGFRA mutations. PDGFRA overexpression is reported in several tumors. However, more notably, mutations (often gain-of-function) or gene amplifications in PDGFRA are key oncogenic events in certain cancer types.
245-	PDH	↓	mitochondrial pyruvate dehydrogenase (PDH)			-an enzyme complex that plays a crucial role in cellular metabolism, particularly in the conversion of pyruvate to acetyl-CoA, which is then used to produce energy in the form of ATP. -key enzyme in cellular metabolism that catalyzes the conversion of pyruvate (produced during glycolysis) into acetyl-CoA, which then enters the tricarboxylic acid (TCA) cycle in the mitochondria. The phosphorylation state of PDH (p-PDH) broadly exists in the cancer cells. Some cancer cells have been found to inhibit PDH activity, which can lead to increased lactate production and a shift towards glycolysis, even in the presence of oxygen. This is known as the Warburg effect. -in cancer cells, PDH has been shown to be inhibited. PDH expression is regulated by various transcription factors, including HIF-1α, c-Myc, and p53.
1290-	PDHA1	↓	Pyruvate Dehydrogenase E1 Alpha 1 Subunit			PDHA1 (Pyruvate Dehydrogenase E1 Alpha 1 Subunit) – PDHA1 encodes the alpha subunit of the pyruvate dehydrogenase (PDH) complex, which is crucial for converting pyruvate into acetyl-CoA. – This step links glycolysis to the tricarboxylic acid (TCA) cycle and oxidative phosphorylation, making PDHA1 a key regulator of cellular energy metabolism. – Proper PDHA1 function supports oxidative metabolism, whereas impaired activity can shift metabolism toward a glycolytic phenotype (commonly referred to as the Warburg effect) in cancer cells. -Low PDHA1 expression or activity may be associated with enhanced glycolysis, leading to increased tumor proliferation and survival under stress. – Clinical Outcome: In several cancer types, reduced PDHA1 levels (or increased PDH inhibition) have been correlated with more aggressive disease and poorer outcomes, suggesting a potential prognostic role.
1301-	PDHB	↓	pyruvate dehydrogenase E1 beta subunit			PDHB (pyruvate dehydrogenase E1 beta subunit) is a component of the pyruvate dehydrogenase (PDH) complex, which plays a key role in the conversion of pyruvate to acetyl-CoA, thereby linking glycolysis with the tricarboxylic acid (TCA) cycle. • Many cancers exhibit metabolic reprogramming (the “Warburg effect”), where there is a shift from oxidative phosphorylation to glycolysis. Some studies have reported a downregulation of PDHB in tumors, which may contribute to this shift.
599-	PDI	↑	Protein Disulfide Isomerase			a family of enzymes that play a crucial role in the folding and assembly of disulfide bond-containing proteins. PDI proteins are typically found in the endoplasmic reticulum (ER), but in cancer cells, they can be expressed on the cell surface, where they can interact with other proteins and influence cell behavior. PDI proteins can promote tumor cell survival by regulating the folding and stability of proteins involved in apoptosis (programmed cell death) and cell stress responses. PDI proteins can contribute to angiogenesis (the formation of new blood vessels) by regulating the activity of vascular endothelial growth factor (VEGF), a key pro-angiogenic factor. PDI-A1: Overexpressed in various types of cancer, including breast, lung, and colon cancer, and associated with poor prognosis.
246-	PDK1	↑	Pyruvate dehydrogenase kinase 1			PDK1 (3-phosphoinositide-dependent protein kinase-1) is a serine/threonine kinase that plays a crucial role in various cellular processes, including cell growth, survival, and metabolism. It is a key component of the PI3K/Akt signaling pathway, which is often dysregulated in cancer. Overexpression or hyperactivation of PDK1 can lead to increased cell proliferation, survival, and resistance to apoptosis, contributing to tumorigenesis. Inhibitors of PDK1 are being explored in preclinical and clinical studies as a means to disrupt cancer cell growth and survival.
1287-	PDK3	↑	Pyruvate Dehydrogenase Kinase 3			Pyruvate Dehydrogenase Kinase 3 (PDK3) – PDK3 is one of the four isoenzymes of pyruvate dehydrogenase kinase (PDK1–4) that phosphorylate and inactivate the pyruvate dehydrogenase (PDH) complex. – By inhibiting PDH, PDK3 reduces the conversion of pyruvate into acetyl-CoA, thereby diverting pyruvate from entry into the tricarboxylic acid (TCA) cycle. – This shift promotes glycolytic metabolism (even under aerobic conditions), a hallmark of the Warburg effect observed in many cancers. – PDK3 is typically upregulated in response to hypoxia or metabolic stress, conditions commonly encountered in the tumor microenvironment. – Its expression can be regulated by hypoxia-inducible factor 1-alpha (HIF-1α) and other metabolic regulators, contributing to the adaptive metabolic reprogramming of cancer cells. – Upregulated Expression: Elevated levels of PDK3 have been observed in several cancer types, including lung, colon, and breast cancers. – Metabolic Reprogramming: Overexpression of PDK3 supports the preferential use of glycolysis over oxidative phosphorylation, allowing cancer cells to adapt to hypoxic conditions and rapid proliferation.
1201-	PDKs	↑	pyruvate dehydrogenase kinase			– PDK1 is often upregulated in cancers and is central to the metabolic reprogramming (Warburg effect) that allows tumor cells to favor glycolysis over oxidative phosphorylation. – Elevated PDK1 expression has been correlated with aggressive tumor behavior and poor prognosis in several cancer types, including non‐small cell lung cancer, ovarian cancer, and gastric cancer. – Although PDK2 has a similar catalytic role as PDK1, its expression levels and impact may vary. – Some studies have observed that increased PDK2 expression is associated with more aggressive cancer features and resistance to therapy in certain tumor types. – PDK3 is often upregulated in response to hypoxic conditions—a common feature of solid tumors—which can further drive metabolic divergence in cancer cells. – The role of PDK4 appears to be more variable. In some settings, its activity might be lower in tumor cells to favor the use of glycolysis, while in others, it may be upregulated as part of broader metabolic adaptations.
1316-	PDT+	↑	PDT+cells			PD-1+Tim-3+terminal CD8+ T cells (PDT+) -In several studies across different malignancies, high frequencies of PD-1⁺Tim-3⁺ terminal CD8⁺ T cells have been associated with advanced disease stages or an immunosuppressive tumor microenvironment. -Their accumulation may correlate with a poorer prognosis, as it reflects chronic immune stimulation and subsequent T cell dysfunction.
870-	Perforin	⇅	Perforin		protein	Perforin is a protein that plays a crucial role in the immune system, particularly in the function of cytotoxic T cells and natural killer cells. These cells are responsible for eliminating infected cells and tumor cells from the body. Perforin is a pore‐forming protein primarily expressed by cytotoxic lymphocytes (natural killer [NK] cells and cytotoxic T lymphocytes). • Its canonical function is to deliver granzymes into target cells (including tumor cells) to trigger apoptosis. • In this sense, perforin is a key mediator of immune surveillance against tumors. In the context of cancer, perforin has been found to have both positive and negative effect In some cases, higher levels of perforin (and accompanying granzyme expression) have been detected in tumors that are “inflamed” or immunologically “hot” – and these are often associated with better immune surveillance. • Note that “expression direction” is best interpreted in the context of TIL density and immune phenotype rather than expression by the tumor cells themselves (which generally do not express perforin Higher levels of perforin expression in the tumor microenvironment (that is, higher abundance of functional CTLs or NK cells) are generally associated with a more favorable prognosis because they reflect active anti-tumor immunity.
617-	PERK	↑	protein kinase-like ER kinase			PERK is a type of kinase that is activated in response to endoplasmic reticulum (ER) stress, which occurs when the ER is overwhelmed with unfolded or misfolded proteins. Once activated, PERK phosphorylates and activates the eukaryotic translation initiation factor 2 alpha (eIF2α), leading to the attenuation of global protein synthesis and the induction of specific genes involved in the UPR. PERK is overexpressed in various types of cancer, including breast, lung, and colon cancer, and that its expression is often associated with poor prognosis. PERK has been shown to have both tumor-suppressive and tumor-promoting roles, depending on the context.
945-	PFK	↑	Phosphofructokinase			PFK (Phosphofructokinase) is a key enzyme in glycolysis, the process by which cells convert glucose into energy. PFK is overexpressed in many types of cancer, and its expression is often associated with poor prognosis. Mechanisms: • PFK promotes glycolysis, which is a key metabolic pathway in cancer cells. • PFK helps to produce energy for cancer cells • PFK promotes cell proliferation. Therapeutic Targeting: • PFK inhibitors are being developed as a potential therapeutic strategy for cancer treatment. • Inhibitors of glycolysis, such as 2-deoxyglucose, are being explored as a potential therapeutic strategy for cancer treatment.
988-	PFK1	↑	Phosphofructokinase-1			Phosphofructokinase-1 (PFK1) is a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. – As a rate-limiting enzyme in glycolysis, PFK1 is subject to complex regulation through allosteric effectors including ATP, AMP, and fructose-2,6-bisphosphate. • Metabolic Control: –PFK1 activity is central to controlling the pace of glycolysis, thereby influencing energy production and intermediary metabolite supply. – In highly proliferative cells or cells under growth conditions, increased glycolytic flux (and, by extension, PFK1 activity) supports the biosynthetic demands of cell division. – Many tumors (including breast, colorectal, and lung cancers) have been reported to have increased PFK1 expression/activity relative to normal tissues. – High glycolytic flux, driven partly by enhanced PFK1, supports rapid cell proliferation and survival in the nutrient/stress-challenged tumor microenvironment. Inhibitors:(typically glycolysis is targeted more broadly) -citrate -Hydrogen ions (pH) – Acidic conditions can have inhibitory effects. -3PO: inhibits PFKFB3, thereby indirectly reducing PFK1 activity. -resveratrol can downregulate glycolytic flux in cancer cells, which may indirectly affect PFK1 activity - FMDs offer an indirect strategy to modulate cancer metabolism by broadly reducing glycolysis. Their impact on PFK1 is likely part of a complex network of metabolic adaptations rather than a direct inhibitory effect.
1144-	PFK2	↑	PFK2			“PFK-2” typically refers to the family of bifunctional enzymes (commonly known as 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatases or PFKFBs) that regulate the levels of fructose-2,6-bisphosphate—a critical allosteric activator of glycolysis. – PFK-2 enzymes catalyze the synthesis of fructose-2,6-bisphosphate (F2,6BP), which in turn is a potent activator of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis. – Increased activity of PFK-2 contributes to enhanced glycolysis and the diversion of glycolytic intermediates into biosynthetic pathways that support rapid tumor cell growth and proliferation. – Upregulated glycolysis supports not only energy production but also the generation of precursors needed for nucleotide, amino acid, and lipid synthesis, aiding tumor progression. – Elevated expression of certain PFK-2 isoforms (notably PFKFB3) has been observed in various cancers such as breast, colorectal, lung, and others. – High PFK-2 expression is frequently associated with increased glycolytic activity, enhanced cell proliferation, and a shift toward an anabolic phenotype, correlating with more aggressive tumor behavior.
1307-	PFKFB2	↑	6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 2			PFKFB2 (6-Phosphofructo-2-Kinase/Fructose-2,6-Bisphosphatase 2) is one of the isoenzymes responsible for regulating the intracellular levels of fructose-2,6-bisphosphate, a key activator of phosphofructokinase-1 (PFK-1) in glycolysis. Its role in cancer metabolism is of increasing interest due to its involvement in regulating glycolytic flux. • In many cancers, increased glycolytic activity is a hallmark. Upregulation of PFKFB2 in some tumors can contribute to this metabolic reprogramming, although expression patterns may be context- and tissue-specific. • Both upregulation and, in some settings, downregulation have been reported, reflecting the enzyme’s complex involvement in metabolic regulation and potential feedback mechanisms within the tumor microenvironment. • Some studies have correlated high PFKFB2 expression with aggressive tumor characteristics, such as increased proliferation, enhanced glycolysis, and potentially poorer clinical outcomes. • In certain cancers, elevated levels of PFKFB2 may indicate a metabolic phenotype that favors tumor growth and resistance to stress, potentially serving as a marker of poor prognosis
770-	PFKL	↑	Phosphofructokinase, Liver		enzyme	PFKL (Phosphofructokinase, Liver) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PFKL is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in the liver. PFKL has been shown to be overexpressed in certain types of tumors, including liver cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells. PFKL is a key regulatory enzyme in the glycolytic pathway. PFKL plays a role in the regulation of glucose metabolism in diabetes.
769-	PFKM	↑	Phosphofructokinase, Muscle		enzyme	PFKM (Phosphofructokinase, Muscle) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. Research has shown that PFKM is overexpressed in various types of cancer, including breast, lung, and colon cancer. PFKM promotes glycolysis and energy production in cancer cells.
771-	PFKP	↑	Phosphofructokinase, Platelet		enzyme	PFKP (Phosphofructokinase, Platelet) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PFKP is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in platelets and other hematopoietic cells. PFKP has been shown to be overexpressed in certain types of tumors, including leukemia and lymphoma. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells. PFKP is a key regulatory enzyme in the glycolytic pathway. PFKP plays a role in the regulation of glucose metabolism in diabetes. PFKP is involved in the regulation of platelet function and thrombosis. – PFKP is one of the isoforms of phosphofructokinase-1 (PFK-1), a key regulatory enzyme in glycolysis that catalyzes the conversion of fructose-6-phosphate to fructose-1,6-bisphosphate. – As a rate-limiting enzyme in glycolysis, PFKP plays a crucial role in controlling the metabolic flux through this pathway, especially in proliferating cells that require higher energy and biosynthetic intermediates. – Upregulated Expression: Many tumors demonstrate an increased expression of PFKP, which is consistent with the observed reliance on glycolysis (even in the presence of oxygen) for rapid energy production and biosynthesis. – Metabolic Reprogramming: The overexpression of PFKP contributes to the enhanced glycolytic rate in cancer cells, supporting tumor growth, survival, and aggressiveness.
607-	PGAM1	↑	Phosphoglycerate mutase 1			Phosphoglycerate mutase 1 (PGAM1) is an enzyme that plays a crucial role in glycolysis. Recent studies have shown that PGAM1 is overexpressed in various types of cancer, and its expression is associated with cancer progression and prognosis.
927-	PGC-1α	↑	Peroxisome proliferator-activated receptor gamma coactivator 1-alpha		transcriptional coactivator	PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) is a transcriptional coactivator that plays a crucial role in regulating cellular energy metabolism, including mitochondrial biogenesis and function. PGC-1α is also involved in various cellular processes, including cell growth, differentiation, and survival. In some cancers (for example, certain melanomas, breast cancers, and prostate cancers), elevated levels of PGC-1α have been observed. – Increased PGC-1α may enhance mitochondrial function and support the energetic and biosynthetic demands of tumor cells, especially under metabolic stress or during metastasis
955-	PGC1A	↑	PPARγ Coactivator 1-alpha			PPARγ Coactivator 1-alpha (PGC1A) is a transcriptional coactivator that plays a crucial role in regulating cellular energy metabolism, including glucose and lipid metabolism. In cancer, PGC1A has been implicated in the regulation of tumor cell metabolism, proliferation, and survival. PGC1A is typically overexpressed and associated with poor prognosis and reduced overall survival in breast, lung, and colon cancers. -PGC1A expression is also associated with increased risk of metastasis and recurrence in various types of cancer.
1029-	PGD2	⇅	prostaglandin D2			PGD2 is one of several prostaglandins produced through the cyclooxygenase (COX) pathway, primarily via the action of hematopoietic and lipocalin-type prostaglandin D synthases (HPGDS and L-PGDS, respectively). It plays roles in inflammation, immune modulation, and cellular signals that can influence tumor development and progression. PGD2 is a prostaglandin with complex roles in cancer biology, mediating processes such as inflammation, immune modulation, and cellular differentiation. In various cancers—including breast, prostate, colorectal, lung, and ovarian cancers—alterations in PGD2 production or PGD2 synthase expression have been reported. Often, higher PGD2 signaling correlates with more favorable outcomes, likely through mechanisms involving anti-inflammatory, pro-differentiation, and pro-apoptotic effects. However, the effects of PGD2 can be context-dependent
247-	PGE1	?	Prostaglandin E1			Prostaglandin E1 (PGE1) is a type of prostaglandin, which is a group of lipid compounds that have various hormone-like effects in the body. PGE1 has been studied for its potential roles in various physiological processes, including inflammation, immune response, and vasodilation. PGE1 is biochemically related to other prostaglandins that play prominent roles in cancer, current literature does not provide a clear picture of its regulation, prognostic associations, or definitive protumorigenic (or antitumorigenic) roles in cancer.
248-	PGE2	↑	Prostaglandin E2			Prostaglandin E2 (PGE2) is a lipid compound that plays a significant role in various physiological processes, including inflammation, immune response, and regulation of cell growth. PGE2 is often found at elevated levels in various types of cancer, including colorectal, breast, and lung cancers. It can promote tumor growth by enhancing cell proliferation, inhibiting apoptosis (programmed cell death), and promoting angiogenesis (the formation of new blood vessels).
460-	PGK1	↑	Phosphoglycerate kinase 1			Phosphoglycerate kinase 1 (PGK1) is the first critical enzyme to produce ATP in the glycolytic pathway. PGK1 is not only a metabolic enzyme but also a protein kinase, which mediates the tumor growth, migration and invasion through phosphorylation some important substrates. PGK1 expression was shown to be significantly upregulated in multiple cancer tissues
358-	PGM1	↑	Phosphoglucomutase 1			Phosphoglucomutase 1 (PGM1) is an enzyme that plays a crucial role in glycogen metabolism. Recent studies have shown that PGM1 is overexpressed in various types of cancer, and its expression is associated with cancer progression and prognosis.
250-	pH	↓				Tumor Microenvironment: Cancer cells often thrive in a more acidic environment compared to normal cells. This is partly due to the metabolic processes of cancer cells, which can produce lactic acid and other acidic byproducts. The acidic microenvironment can promote tumor growth and invasion. Many tumors exhibit an acidic microenvironment. This is largely due to the high rate of glycolysis (often referred to as the Warburg effect), even in the presence of oxygen, leading to lactate production. Acidification is thought to promote invasion, metastasis, and resistance to certain chemotherapies. The body maintains a relatively stable pH in the blood (around 7.4). However, the pH of tissues can vary, and tumors can exhibit a lower pH. -normal tissues have a higher extracellular pH than intracellular pH, in cancer is exactly the opposite. (inversion of the pH gradient) Cancer cells often overexpress proton pumps (such as V-ATPase) and transporters that actively extrude protons (H⁺) to maintain an intracellular pH conducive to their growth. Inhibiting these pumps can lead to intracellular acidification and potentially induce apoptosis or render cancer cells more vulnerable to other treatments.
936-	PHDs	↓	Prolyl Hydroxylases			Prolyl Hydroxylases (PHDs) are a family of enzymes that play a crucial role in regulating the activity of the transcription factor hypoxia-inducible factor (HIF). PHDs are responsible for hydroxylating specific proline residues on HIF, which leads to its degradation and prevents its activation. Generally low expression in cancers, with poor prognosis.
251-	PHF6	↓	PHD finger protein 6	CGL-Driver Genes	TSG	PHF6 (PHD finger protein 6) is a gene that encodes a protein involved in various cellular processes, including transcriptional regulation and chromatin remodeling. PHF6 is a gene with tumor-suppressive functions that is frequently altered (usually by loss-of-function mutations or decreased expression) in several hematologic malignancies such as T-ALL and AML. Its inactivation is generally associated with features of aggressive disease and poor prognostic indicators. In solid tumors, more research is necessary to define the exact clinical implications. Overall, a normal PHF6 function appears crucial for proper chromatin regulation and gene expression, and its disruption contributes to oncogenic processes through deregulated transcription and impaired differentiation.
252-	PI3K	↑	Phosphatidylinositide-3-Kinases	HalifaxProj(inhibit) CGL-CS		Phosphatidylinositol 3-kinase (PtdIns3K or PI3K) is a family of enzymes that play a crucial role in cell signaling pathways, particularly in the regulation of cell growth, survival, and metabolism. The PI3K pathway is one of the most frequently altered pathways in human cancer. Inhibition of the PI3K pathway has been explored as a therapeutic strategy for cancer treatment. Several PI3K inhibitors have been developed and are currently being tested in clinical trials. These inhibitors can target specific components of the pathway, such as PI3K, AKT, or mTOR. Class I phosphoinositide 3-kinase (PI3K) Class III PtdIns3K In contrast to the class III PtdIns3K as a positive regulator of autophagy, class I PI3K-AKT signaling has an opposing effect on the initiation of autophagy. PI3K inhibitors include: -Idelalisib , Copanlisib, Alpelisib -LY294002? -Wortmannin: potent PI3K inhibitor, has some associated toxicity. -Quercetin: -Curcumin -Resveratrol -Epigallocatechin Gallate (EGCG)
253-	PI3K/Akt	↑	PI3K/Akt signaling	HalifaxProj(inhibit) TCGA		The PI3K/Akt signaling pathway plays a crucial role in various cellular processes, including growth, proliferation, survival, and metabolism. Pathway Components: Phosphoinositide 3-kinases (PI3Ks): A family of enzymes that phosphorylate the inositol ring of phosphatidylinositol, leading to the production of phosphatidylinositol (3,4,5)-trisphosphate (PIP3). Akt (Protein Kinase B): A serine/threonine kinase that is activated by PIP3. Once activated, Akt phosphorylates various substrates involved in cell survival and growth. Overactivation can lead to uncontrolled cell growth. Angiogenesis: Akt can promote the expression of pro-angiogenic factors, facilitating the formation of new blood vessels to supply tumors with nutrients and oxygen.
254-	PI3k/Akt/mTOR	↑	Phosphoinositide 3-kinase/Protein Kinase B/ mammalian target of rapamycin			The PI3K/Akt/mTOR signaling pathway is a critical regulator of cell growth, proliferation, survival, and metabolism. In many cancers (such as breast, colorectal, lung, and endometrial cancers), the PI3K/Akt/mTOR pathway is often hyperactivated. – This hyperactivation is frequently due to gene mutations (e.g., in PIK3CA), loss of PTEN, and amplification events that enhance the pathway’s activity. – Increased activity is also observed via elevated levels of phosphorylated Akt and mTOR in tumors compared to normal tissues
255-	PI3K/mTOR/ETS2	↑	PI3K/mTOR/ETS2 pathway			The PI3K/Akt/mTOR signaling pathway is a critical cellular signaling pathway that regulates various cellular processes, including growth, proliferation, survival, and metabolism. In some cancers, there is an overexpression of PI3K, which can enhance signaling through the pathway even in the absence of growth factor stimulation. Increased expression of Akt isoforms (Akt1, Akt2, and Akt3) has been observed in several cancers. Both mTORC1 and mTORC2 can be overexpressed in tumors.
662-	PIAS-3	↓	Protein Inhibitor of Activated STAT-3			PIAS-3 (Protein Inhibitor of Activated STAT-3) is a protein that plays a crucial role in regulating various cellular processes, including cell growth, differentiation, and survival. In the context of cancer, PIAS-3 has been found to have both tumor-suppressing and tumor-promoting effects, depending on the type of cancer and the specific cellular context. In several cancers (e.g., glioblastoma, breast cancer, and lung cancers), reduced levels of PIAS3 have been reported. – Downregulation of PIAS3 can result in unchecked STAT3 activity, which contributes to tumor progression and therapeutic resistance.
1182-	Piezo1	↑	Piezo1			Piezo1 is a mechanosensitive ion channel that converts mechanical stimuli into electrochemical signals. Piezo1 protein is a mechanosensitive ion channel that allows intracellular calcium influx in response to various mechanical signals such as static pressure, shear stress, and membrane stretch and further initiates downstream biological responses. It is critical in various physiological processes, including the development of vasculatures, regulation of red blood cell volume, and sensation of light touch. Piezo1 is also highly expressed in the bone, regulating the differentiation of mesenchymal stem cells and mediating calcium ion influx in osteocytes and osteoblasts In a number of cancer types (such as breast, colon, and prostate cancer), studies have found that Piezo1 is often upregulated. An increase in Piezo1 expression can promote enhanced cell migration and invasive behavior, both of which are critical for cancer spread.
256-	PIK3CA	↑	phosphoinositide-3-kinase, catalytic, alpha polypeptide	CGL-Driver Genes	Oncogene	Class III PtdIns3K (PIK3C3/Vps34) Class I phosphoinositide 3-kinase (PI3K) In contrast to the class III PtdIns3K as a positive regulator of autophagy, class I PI3K-AKT signaling has an opposing effect on the initiation of autophagy. PIK3CA is a gene that encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), which is a key player in the PI3K/AKT signaling pathway. This pathway is crucial for various cellular processes, including growth, proliferation, survival, and metabolism. PIK3CA is often overexpressed, which can lead to increased activity of the PI3K/AKT signaling pathway. This overexpression can contribute to tumor growth, survival, and metastasis. Class III PtdIns3K (PIK3C3/Vps34) is central to autophagy regulation. In many tumor types, higher expression is thought to promote autophagy, which can help cancer cells survive under metabolic and therapeutic stress. This survival advantage is one reason why high PIK3C3 expression sometimes correlates with a more aggressive phenotype and poorer overall prognosis.
734-	PIK3R1	↑	PIK3R1/p85S6 Phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1)			p85S6, also known as phosphatidylinositol 3-kinase regulatory subunit alpha (PIK3R1), is a protein that plays a crucial role in the regulation of cell growth, survival, and metabolism. It is a subunit of the phosphatidylinositol 3-kinase (PI3K) enzyme, which is involved in the PI3K/AKT signaling pathway. The PI3K/AKT pathway is a key regulator of cell proliferation, differentiation, and survival. PIK3R1 overexpressed in: breast, lung, colon, prostate, pancreatic, liver, stomach, esophageal, head and neck, thyroid, melanoma, endometrial, cervical, bladder, RCC.
1209-	Pin1	↑	Peptidyl-prolyl cis-trans isomerase, NIMA-interacting 1			Pin1 (Peptidyl-prolyl cis-trans isomerase, NIMA-interacting 1) is a peptidyl-prolyl isomerase that specifically recognizes phosphorylated serine/threonine-proline motifs, thereby modulating the conformation and function of various proteins. This post-phosphorylation regulation can directly affect cell division, survival, and metastasis—all of which impact cancer progression high Pin1 expression in breast, pca, had and lung cancers is associated with more aggressive tumor behavior, increased metastatic potential, and poorer overall survival. Inhibitors: -Juglone (5-hydroxy-1,4-naphthoquinone) is one of the most widely studied natural inhibitors of Pin1. -All‑trans Retinoic Acid (ATRA) A metabolite of vitamin A, ATRA has been reported to inhibit Pin1 activity. -EGCG -Curcumin (Proposed) juglone is thought to act via direct covalent modifications of Pin1, whereas ATRA and EGCG likely interact through non-covalent binding.
1239-	PINK1	↓	PTEN-induced kinase 1			PINK1 (PTEN-induced kinase 1) is a mitochondrial kinase that plays a critical role in maintaining mitochondrial quality control through mitophagy. - many studies indicate that lower PINK1 expression tends to correlate with more aggressive disease and poorer prognosis—likely due to compromised mitochondrial quality control
1280-	PIP3	↑	Phosphatidylinositol (3,4,5)-trisphosphate			PIP3 is a key lipid second messenger that plays a central role in the PI3K/AKT signaling pathway – Increased PIP3 levels are a hallmark of cancers characterized by PI3K pathway activation. – Mutations or amplifications in PI3K subunits and loss of PTEN function often result in sustained PIP3 production, thereby driving oncogenic processes. – Elevated PIP3 signaling contributes to increased cell proliferation, survival, metabolic reprogramming, and metastatic potential.
752-	PIR	↑	Phosphoinositide-interacting regulator of TRP channels		protein	PIR (Phosphoinositide-interacting regulator of TRP channels) is a protein that has been implicated in the regulation of various cellular processes, including cell growth, survival, and migration. PIR has been found to be overexpressed in several types of cancer, including breast, lung, colon, and prostate cancer. PIR has been shown to promote cell growth and survival by regulating the activity of various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways.
753-	Pirin	↑	Pirin		protein	Pirin is a protein that has been implicated in the regulation of various cellular processes, including cell growth, differentiation, and survival. Pirin has been found to be overexpressed in several types of cancer, including breast, lung, colon, and prostate cancer. Pirin has been shown to promote cell growth and survival by regulating the activity of various signaling pathways, including the PI3K/AKT and MAPK/ERK pathways.
1194-	PKA	↑	protein kinase A			protein kinase A (PKA) • PKA is composed of regulatory (R) and catalytic (C) subunits. Binding of cAMP to the regulatory subunits releases the catalytic subunits, which then phosphorylate target proteins. – Increased PKA activity has been associated with the activation of downstream signaling pathways that promote cell growth and survival. – Thus, the level of PKA activation (often indirectly inferred by phosphorylation status of downstream targets) can serve as a marker for tumor progression and treatment resistance. – PKA does not act in isolation—it interacts with other signaling pathways (e.g., MAPK, PI3K/AKT).
1021-	PKCδ	⇅	Protein Kinase C delta			PKCδ is one of the novel isoforms of the Protein Kinase C (PKC) family, involved in regulating various cellular processes. It participates in diverse signaling pathways influencing cell proliferation, differentiation, survival, apoptosis, and migration. In some cancers, PKCδ is upregulated and associated with higher tumor aggressiveness, particularly when it contributes to pathways that promote cell survival and invasion. Conversely, in other contexts, PKCδ has been reported to act as a tumor suppressor where its activation can promote apoptosis or inhibit cell proliferation.
1302-	PKL	?	liver isoform of pyruvate kinase			PKL refers to the liver isoform of pyruvate kinase, an enzyme that catalyzes the final step of glycolysis • PKL is normally highly expressed in liver tissue and is involved in efficiently channeling glycolytic intermediates into pyruvate and subsequently into energy production pathways. • In cancer, metabolic reprogramming (the Warburg effect) is widespread. While many tumors adopt the PKM2 isoform to support rapid proliferation, alterations in PKL expression have been observed particularly in liver cancers, and some extrahepatic tumors where pancreatic or biliary differentiation is involved.
1306-	PKM1	?	pyruvate kinase muscle isoform 1			PKM1 (pyruvate kinase muscle isoform 1) is one of the isoenzymes of pyruvate kinase that drives the final step of glycolysis by converting phosphoenolpyruvate to pyruvate, with concomitant ATP production. Unlike PKM2, which is well known for its role in cancer metabolism (often favoring anabolic processes and rapid proliferation), PKM1 is constitutively active and promotes a more oxidative metabolism. • In many cancers, a metabolic switch is observed where PKM2 is preferentially expressed to allow for metabolic flexibility and support biosynthetic needs. As a result, PKM1 is less frequently expressed in these tumor types. • However, some studies have reported contexts in which a higher PKM1/PKM2 ratio is observed, which might be associated with a more oxidative and less proliferative metabolic state.
772-	PKM2	↑	Pyruvate Kinase, Muscle 2		enzyme	<b>PKM2</b> (Pyruvate Kinase, Muscle 2) is an enzyme that plays a crucial role in glycolysis, the process by which cells convert glucose into energy. PKM2 is a key regulatory enzyme in the glycolytic pathway, and it is primarily expressed in various tissues, including muscle, brain, and cancer cells.<br> -C-myc is a common oncogene that enhances aerobic glycolysis in the cancer cells by transcriptionally activating GLUT1, HK2, PKM2 and LDH-A<br> -PKM2 has been shown to be overexpressed in many types of tumors, including breast, lung, and colon cancer. This overexpression may contribute to the development and progression of cancer by promoting glycolysis and energy production in cancer cells.<br> -PK exists in four isoforms: PKM1, PKM2, PKR, and PKL<br> -PKM2 plays a role in the regulation of glucose metabolism in diabetes.<br> -PKM2 is involved in the regulation of cell proliferation, apoptosis, and autophagy.<br> – Pyruvate kinase catalyzes the final, rate-limiting step of glycolysis, converting phosphoenolpyruvate (PEP) to pyruvate with the production of ATP.<br> – The PKM2 isoform is uniquely regulated and can exist in both highly active tetrameric and less active dimeric forms.<br> – Cancer cells often favor the dimeric form of PKM2 to slow pyruvate production, thereby accumulating upstream glycolytic intermediates that can be diverted into anabolic pathways to support cell growth and proliferation.<br> – Under low oxygen conditions, cancer cells rely on altered metabolic pathways in which PKM2 is a key player. – The shift to aerobic glycolysis (Warburg effect) orchestrated in part by PKM2 helps tumor cells survive and grow in hypoxic conditions.<br> <br> – Elevated expression of PKM2 is frequently observed in many cancer types, including lung, breast, colorectal, and pancreatic cancers.<br> – High levels of PKM2 are often correlated with enhanced tumor aggressiveness, poor differentiation, and advanced clinical stage.<br> <br> <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC5746412/">PKM2 in carcinogenesis and oncotherapy</a><br> <br> Inhibitors of PKM2:<br> -Shikonin, Resveratrol, Baicalein, EGCG, Apigenin, Curcumin, Ursolic Acid, Citrate (best known as an allosteric inhibitor of phosphofructokinase-1 (PFK-1), a key rate-limiting enzyme in glycolysis) potential to directly inhibit or modulate PKM2 is less well established<br> <br> <a href="https://nestronics.ca/dbx/tbResList.php?rfv=%25&rmsv=%25&lcsv=%25&ctsv=&bdh=%25&qv=&qv2=&tsv=772&ssv=%25&esv=%25&fi=0">Full List of PKM2 inhibitors from Database</a><br> -key connected observations: Glycolysis↓, lactateProd↓, ROS↑ in cancer cell, while some result for opposite effect on normal cells. <br> <a href="https://pmc.ncbi.nlm.nih.gov/articles/PMC8292966/">Tumor pyruvate kinase M2 modulators</a><br> <br> <a href="https://pubmed.ncbi.nlm.nih.gov/25798688/">Flavonoids effect on PKM2</a><br> Compounds name IC50/AC50uM Effect <br> Flavonols <br> 1. Fisetin 0.90uM Inhibition <br> 2. Rutin 7.80uM Inhibition <br> 3. Galangin 8.27uM Inhibition <br> 4. Quercetin 9.24uM Inhibition <br> 5. Kaempferol 9.88uM Inhibition <br> 6. Morin hydrate 37.20uM Inhibition <br> 7. Myricetin 0.51uM Activation <br> 8. Quercetin 3-b- D-glucoside 1.34uM Activation <br> 9. Quercetin 3-D -galactoside 27-107uM Ineffective <br> Flavanons <br> 10. Neoeriocitrin 0.65uM Inhibition <br> 11. Neohesperidin 14.20uM Inhibition <br> 12. Naringin 16.60uM Inhibition <br> 13. Hesperidin 17.30uM Inhibition <br> 14. Hesperitin 29.10uM Inhibition <br> 15. Naringenin 70.80uM Activation <br> Flavanonols <br> 16. (-)-Catechin gallateuM 0.85 Inhibition <br> 17. (±)-Taxifolin 1.16uM Inhibition <br> 18. (-)-Epicatechin 1.33uM Inhibition <br> 19. (+)-Gallocatechin 4-16uM Ineffective <br> Phenolic acids <br> 20. Ferulic 11.4uM Inhibition <br> 21. Syringic and 13.8uM Inhibition <br> 22. Caffeic acid 36.3uM Inhibition <br> 23. 3,4-Dihydroxybenzoic acid 78.7uM Inhibition <br> 24. Gallic acid 332.6uM Inhibition <br> 25. Shikimic acid 990uM Inhibition <br> 26. p-Coumaric acid 22.2uM Activation <br> 27. Sinapinic acids 26.2uM Activation <br> 28. Vanillic 607.9uM Activation <br>
1291-	PKM2:PKM1	↑	PKM2/PKM1 ratio			PKM2/PKM1 ratio -PKM (pyruvate kinase M) exists mainly as two splice isoforms: PKM1 and PKM2. -PKM1 is constitutively active and typically found in tissues with high-energy demands (e.g., muscle, brain). -PKM2 is less active under some conditions and is highly regulated; importantly, it is often upregulated in cancers. - A higher PKM2/PKM1 ratio is thought to promote the “Warburg effect” (aerobic glycolysis) that benefits rapidly proliferating tumor cells by providing biosynthetic precursors even though it is less energy efficient. -An increased PKM2/PKM1 ratio has been associated with enhanced tumor cell proliferation, survival, and metastasis.
401-	PLC	?	perlecan			Perlecan is overexpressed in the desmoplastic prostate cancer stroma. knockdown of perlecan in metastatic prostate cancer cells reduces in vivo tumor growth. also known as basement membrane-specific heparan sulfate proteoglycan core protein (HSPG) or heparan sulfate proteoglycan 2 (HSPG2), is a protein that in humans is encoded by the HSPG2 gene.
574-	PleEff	↑	pleural effusion			A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung.
747-	PLEKHM3	↑				PLEKHM3 is a protein-coding gene that has been associated with various types of cancer. The PLEKHM3 gene encodes a protein that is involved in the regulation of cell growth, division, and survival. Research has shown that PLEKHM3 is overexpressed in several types of cancer, including breast cancer, lung cancer, and colon cancer. Overexpression of PLEKHM3 has been linked to increased cell proliferation, tumor growth, and metastasis.
550-	PLIN1	?	Perilipin 1			Perilipins, including PLIN1, PLIN2, PLIN3, PLIN4, PLIN5, is a family of lipid droplet-associated proteins that participate in lipid metabolism regulation.
1277-	polyA	↑	polyamine		marker	Polyamines—organic cations such as putrescine, spermidine, and spermine—play fundamental roles in cell growth and proliferation. -They are synthesized from amino acid precursors via key enzymes such as ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase. -Enzymes such as ODC are frequently found to be overexpressed in malignant tissues, driving increased synthesis of polyamines. – Many cancers exhibit increased polyamine levels, either through upregulated biosynthetic pathways or decreased catabolism. – Elevated Polyamine Levels: Numerous studies have shown that high levels of polyamines are present in various cancers, including colorectal, prostate, breast, and liver cancers. Measurements can be performed in tumor tissues or in body fluids such as urine, serving as potential non-invasive biomarkers.
1273-	PONs	↑	paraoxonase			Paraoxonases refer to a family of enzymes—primarily PON1, PON2, and PON3—that are involved in the detoxification of oxidized lipids and the metabolism of various xenobiotics. Their roles in modulating oxidative stress and inflammation have attracted attention in cancer research. -Upregulation in Some Tumors: In certain cancer types, elevated expression of paraoxonase enzymes may occur as an adaptive response to increased oxidative stress. For instance, some tumors demonstrate increased levels of PON2, which could help protect cancer cells from oxidative damage.
258-	Poor perfusion	?		HalifaxProj(improve)		Poor perfusion refers to inadequate blood flow to tissues, which can lead to a variety of complications, especially in patients with cancer. Cancerous tumors often develop in a way that disrupts normal blood flow. The rapid growth of tumors can outpace the development of new blood vessels (angiogenesis), leading to areas of poor perfusion within the tumor. This can result in hypoxia (low oxygen levels) in tumor cells, which can promote aggressive tumor behavior and resistance to therapy.
993-	PPARα	⇅	Peroxisome Proliferator-Activated Receptor Alpha			• PPARα – Regulates fatty acid oxidation, lipid metabolism, and energy homeostasis. – Expressed primarily in liver, heart, kidney, and muscle, PPARα activation induces genes involved in β-oxidation and lipid transport. – It is also involved in modulating inflammatory responses, which may indirectly affect cellular proliferation and survival. – Expression and activation in cancers can vary: – In some liver cancers, PPARα expression or activity may be altered, reflecting its central role in hepatic metabolism. – Overactivation has been associated with liver proliferation in rodent models; however, species differences exist regarding the carcinogenic potential of PPARα agonists. – Outside the liver, PPARα’s role is less defined, but its regulation of inflammation and lipid metabolism may influence tumor metabolism and microenvironment.
259-	PPARγ	↑	Peroxisome proliferator-activated receptor gamma (PPAR-γ or PPARG)			Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a type of nuclear receptor that plays a crucial role in regulating various biological processes, including glucose metabolism, lipid metabolism, and inflammation. It is primarily expressed in adipose tissue, but it is also found in other tissues, including the colon, breast, and prostate. PPAR-γ has been shown to have both tumor-suppressive and tumor-promoting effects, depending on the type of cancer and the context. In some cancers, activation of PPAR-γ can inhibit cell proliferation and induce apoptosis, while in others, it may promote tumor growth. PPARγ – Plays a central role in adipogenesis, lipid storage, and insulin sensitivity. – Widely expressed in adipose tissue, but also present in colon, breast, and immune cells. – In addition to metabolic functions, PPARγ regulates cell differentiation, apoptosis, and has anti-inflammatory effects. – Ligand binding (such as endogenous fatty acids or synthetic agonists like thiazolidinediones) alters transcriptional programs impacting cell cycle and survival. – In many cases, PPARγ is expressed in tumor cells, and its activation has been linked to induction of differentiation and growth arrest. – However, expression levels can differ based on tumor subtype, with some studies reporting elevated levels while others note reductions in aggressive tumors. – Crosstalk with other signaling pathways (e.g., Wnt/β-catenin, MAPK) can alter PPARγ's net effect in cancer cells.
948-	PPP	↑	pentose phosphate pathway			The pentose phosphate pathway (PPP) is a metabolic pathway that generates NADPH and pentoses from glucose-6-phosphate. In cancer, the PPP is often upregulated to support the increased demand for NADPH, which is necessary for fatty acid synthesis, antioxidant defenses, and maintaining the balance of redox reactions. High expression of PPP enzymes is often associated with poor prognosis in various cancers, including breast, lung, colorectal, prostate, pancreatic, and ovarian cancer.
260-	PPP2R1A	↓	protein phosphatase 2 (formerly 2A), regulatory subunit A, alpha isoform	CGL-Driver Genes	Oncogene	PPP2R1A (Protein Phosphatase 2 Regulatory Subunit A) is a gene that encodes a regulatory subunit of protein phosphatase 2A (PP2A), which is a critical enzyme involved in various cellular processes, including cell growth, division, and apoptosis. PP2A is considered a tumor suppressor, and its activity is often reduced in cancer cells. PP2A and PPP2R1A are often used interchangeably in the literature, but technically, PP2A refers to the enzyme itself, while PPP2R1A refers to the gene that encodes one of the subunits of the enzyme.
938-	PR	↓	Progesterone receptor			Progesterone receptor (PR) expression is observed in various types of cancer, and its prognostic significance can vary depending on the cancer type. progesterone receptor (PR) is often downregulated in various types of cancer. PR expression in cancer is generally associated with a better prognosis, as these tumors tend to be more differentiated and less aggressive.
427-	PRAS40	↑	proline-rich Akt substrate of 40 kDa			The phosphorylation of PRAS40 is often associated with the tumor progression of melanoma, prostate cancer, etc. Elevated PRAS40-Thr 246 phosphorylation has been reported in several cancer cell lines PRAS40 serves as an important mediator linking Akt signaling to mTORC1 activation. In many cancers—such as breast, lung, and colorectal—enhanced Akt activity leads to increased phosphorylation of PRAS40, thereby promoting tumor cell survival, proliferation, and growth. These changes are often associated with more aggressive tumor behavior and poorer outcomes.
478-	pRB	↓	retinoblastoma protein	Tumor suspressor		pRB, or retinoblastoma protein, is a crucial tumor suppressor that plays a significant role in regulating the cell cycle. It is encoded by the RB1 gene, and its primary function is to control the progression of cells from the G1 phase to the S phase of the cell cycle. When functioning properly, pRB binds to and inhibits E2F transcription factors, which are necessary for the expression of genes required for DNA synthesis and cell division. pRB is often found to be downregulated or functionally inactivated due to mutations in the RB1 gene or through other mechanisms.
833-	PRC2	↑	Polycomb repressive complex 2			Polycomb repressive complex 2 (PRC2) is a key epigenetic regulator that plays a crucial role in maintaining cellular identity and suppressing tumor formation. PRC2 is a histone methyltransferase complex that catalyzes the trimethylation of histone H3 lysine 27 (H3K27me3), a repressive epigenetic mark that silences gene expression. PRC2 is composed of four core subunits: EZH2 (enhancer of zeste homolog 2), SUZ12, EED, and RbAp46/48. PRC2 is often overexpressed or mutated, leading to aberrant epigenetic regulation and contributing to tumorigenesis. EZH2, the catalytic subunit of PRC2, is often overexpressed in various types of cancer
261-	PRDM1	↓	PR domain containing 1, with ZNF domain	CGL-Driver Genes	TSG	PRDM1, also known as PR domain containing 1, with ZNF domain, is a gene that encodes a protein involved in various cellular processes, including differentiation, development, and immune response. PRDM1 has been studied for its dual role as a tumor suppressor and, in some cases, as an oncogene. PRDM1 is a critical transcription factor whose normal function is associated with cell differentiation and the shutdown of proliferative programs. In several B-cell malignancies, PRDM1 is frequently altered by mutations or reduced expression, and these changes are generally associated with a worse prognosis—supporting its role as a tumor suppressor. In other cancers, the patterns of expression and functional consequences appear more variable, underscoring the need for further research to fully understand its context-specific roles in tumorigenesis
263-	PRDX	↑	Peroxiredoxin			also known as Prx Peroxiredoxins are endogenous antioxidants and redox sensors. Properties of the peroxiredoxins make them suitable as markers of oxidative stress. Peroxiredoxins (Prxs) are a family of antioxidant enzymes that play a crucial role in cellular redox signaling and the detoxification of reactive oxygen species (ROS). They are involved in various cellular processes, including cell proliferation, differentiation, and apoptosis. Prx isoforms (such as Prx1 and Prx4) are often overexpressed. This overexpression can help cancer cells cope with increased levels of reactive oxygen species (ROS) generated during rapid cell division and metabolic changes. Elevated Prx levels have been linked to resistance against chemotherapy and radiation therapy. For example, Prx2 and Prx3 have been implicated in protecting cancer cells from oxidative damage caused by these treatments. Some Prxs, such as Prx3, can act as tumor suppressors. Their downregulation or loss of function has been associated with increased tumorigenesis and poor prognosis in certain cancers. PRDX family comprises several isoforms (for example, PRDX1, PRDX2, PRDX3, etc.) that function as antioxidant enzymes to reduce reactive oxygen species (ROS) and maintain redox balance. PRDX family—especially key isoforms like PRDX1 and PRDX2—are often upregulated in various cancers, correlating with worse prognosis and enhanced tumor cell survival. Through their ROS-detoxifying capabilities, these proteins generally play protumorigenic roles by protecting malignant cells from oxidative stress and supporting resistance to apoptosis and therapy.
1213-	PRDX4	↑	Peroxiredoxin 4			Peroxiredoxin 4 (PRDX4) is one of the members of the peroxiredoxin family of antioxidant enzymes. It plays a key role in reducing hydrogen peroxide and other peroxides, thereby contributing to the maintenance of the intracellular redox balance. In addition to its antioxidant function, PRDX4 is located in the endoplasmic reticulum (and can be secreted), which adds complexity to its role in cellular homeostasis, stress responses, and cancer biology. – Several studies have reported that PRDX4 is overexpressed in various cancers, including lung, breast, prostate, and gastrointestinal cancers. – In some cases, increased PRDX4 levels are thought to reflect a cellular adaptation to elevated oxidative stress in the tumor microenvironment. – High PRDX4 expression has been observed to correlate with more aggressive tumor phenotypes in particular cancer types. This may be due to its role in protecting cancer cells from oxidative damage, thereby supporting cell survival and growth under stress conditions. – In some studies, increased PRDX4 has been linked to enhanced tumor progression, metastasis, and resistance to therapy.
759-	PRDX6	⇅	Peroxiredoxin 6		protein	PRDX6 (Peroxiredoxin 6) is a protein that plays a crucial role in maintaining cellular redox balance and protecting cells from oxidative damage. PRDX6 has been found to have both tumor-suppressive and tumor-promoting roles, depending on the type of cancer and the cellular context. PRDX6 can neutralize reactive oxygen species (ROS)
714-	PRKCG	↑	Protein Kinase C Gamma			PRKCG (Protein Kinase C Gamma) is a gene that encodes a protein involved in cell signaling pathways.PRKCG plays a role in various cellular processes, including cell growth, differentiation, and survival. Overexpressed in: Brain tumors, breast, CRC, Lung
926-	proApCas	↓	proapoptotic cascade			Proapoptotic cascade markers are proteins or molecules that indicate the activation of the apoptotic pathway, which is a series of cellular events leading to programmed cell death. Some common proapoptotic cascade markers include: • Caspase-3: • Caspase-8: • Caspase-9: • Cytochrome c: is released into the cytosol during apoptosis, triggering the activation of caspase-9 • Bax: a proapoptotic Bcl-2 family protein that promotes mitochondrial outer membrane permeabilization • Bak: a proapoptotic Bcl-2 family protein that promotes mitochondrial outer membrane permeabilization • Bid: a proapoptotic Bcl-2 family protein that is cleaved by caspase-8, leading to the activation of the intrinsic apoptotic pathway • PARP-1: a DNA repair enzyme that is cleaved by caspase-3, leading to the inhibition of DNA repair and the promotion of apoptosis • Annexin V: a protein that binds to phosphatidylserine, a phospholipid that is exposed on the surface of apoptotic cells • p53: a tumor suppressor protein that can induce apoptosis in response to DNA damage or other forms of cellular stress. a functional proapoptotic cascade acts as a natural barrier to tumorigenesis by ensuring that cells with damaging mutations or stressful conditions are eliminated. In many cancers, defects—in terms of gene mutations, expression changes, or regulatory blockades—within this cascade correlate with more aggressive disease, poorer prognosis, and resistance to therapy
1166-	PRODH	↓	proline dehydrogenase			PRODH (also known as proline oxidase) is a mitochondrial enzyme that catalyzes the first step in proline degradation, linking proline metabolism to energy production and redox regulation. – PRODH catalyzes the oxidation of proline to pyrroline-5-carboxylate (P5C) within the mitochondria. – This reaction contributes electrons to the electron transport chain, potentially influencing ATP production. - Redox Regulation and ROS Generation: – During proline oxidation, PRODH activity can generate reactive oxygen species (ROS). – Proline can serve as a source of energy under metabolic stress. – The enzyme proline dehydrogenase (PRODH) initiates proline catabolism, converting it into pyrroline-5-carboxylate (P5C) and influencing the mitochondrial redox state. – This process is linked to the generation of reactive oxygen species (ROS), which may either signal adaptive responses or promote apoptosis depending on context. – Proline metabolism is intertwined with cellular redox balance. PRODH activity can contribute to ROS production, potentially triggering stress responses in tumor cells. – Upregulation of PRODH and the resultant ROS production can induce apoptosis in some contexts, acting as a tumor suppressive mechanism. – Elevated PRODH activity or expression can promote ROS generation to levels that trigger apoptosis, thereby limiting tumor growth. – Some studies have demonstrated that higher PRODH expression in tumor cells is associated with increased apoptosis and potentially better prognosis. – Strategies that enhance PRODH activity might be harnessed to promote ROS-induced apoptosis in select cancers, whereas in other contexts, inhibiting PRODH might be beneficial if tumor cells rely on its metabolic output under stress conditions.
1165-	proline	↑	proline			Proline, a non-essential amino acid, plays multiple roles in cellular function, including protein synthesis, energy metabolism, and redox balance. – Proline is a key component in the structure of proteins (notably collagen) and influences protein folding due to its unique cyclic structure. – Its availability is critical for extracellular matrix synthesis, which is important for tumor stroma remodeling and metastasis. The effect of proline on the metabolism of tumor cells seems to be particularly important, where a significant increase in the concentration of this amino acid is observed in comparison with normal cells. The high concentration of intracellular proline is associated with an enhanced ability of tumor cells to metastasize. – Proline can serve as a source of energy under metabolic stress. – The enzyme proline dehydrogenase (PRODH) initiates proline catabolism, converting it into pyrroline-5-carboxylate (P5C) and influencing the mitochondrial redox state. – This process is linked to the generation of reactive oxygen species (ROS), which may either signal adaptive responses or promote apoptosis depending on context. – Proline metabolism is intertwined with cellular redox balance. PRODH activity can contribute to ROS production, potentially triggering stress responses in tumor cells. – Upregulation of PRODH and the resultant ROS production can induce apoptosis in some contexts, acting as a tumor suppressive mechanism.
1243-	Prot	?	Protein Levels
262-	Proteasome	↑	Proteasome	HalifaxProj (inhibit)		The proteasome is a crucial component of the cellular machinery responsible for degrading ubiquitinated proteins, which are proteins tagged for destruction. This process is essential for maintaining cellular homeostasis, regulating the cell cycle, and controlling various signaling pathways. Many cancer cells exhibit increased expression of proteasome subunits. This upregulation can enhance the proteasome's capacity to degrade proteins, including those that regulate cell cycle progression and apoptosis, thereby promoting tumor growth and survival. Proteasome inhibitors act by blocking the activity of the proteasome, a crucial cellular complex responsible for degrading most intracellular proteins. -The proteasome is responsible for degrading ubiquitin-tagged proteins, including misfolded, damaged, or regulatory proteins. By inhibiting the proteasome’s function, these proteins accumulate within the cell. -Accumulated proteins can lead to increased cellular stress, particularly in the endoplasmic reticulum (ER) where misfolded proteins build up. This stress can trigger the unfolded protein response (UPR), which, if unresolved, may lead to apoptosis (programmed cell death). -It is well known that ROS plays an important role in proteasome inhibition-induced cell death Inhibitor Drugs: bortezomib (Velcade) and carfilzomib Natural Product Inhibitors: -Gambogic Acid: https://nestronics.ca/dbx/tbResEdit.php?rid=1960 -Lactacystin: Origin: Isolated from the bacterium Streptomyces lactacystinaeus. -Epoxomicin is a highly selective and potent inhibitor of the proteasome. Its structure has informed the design of synthetic drugs such as carfilzomib -Syringolin A -Tyropeptins -EGCG -Withania somnifera (commonly known as Ashwagandha). -Celastrol Origin: Derived from plants of the Tripterygium genus (commonly known as Thunder God Vine).
1084-	PrxI	↑	Peroxiredoxin I			Prx I is an endogenous protein—one of the six members of the peroxiredoxin family. • It is naturally expressed in cells and plays a role in antioxidant defense by reducing hydrogen peroxide and organic hydroperoxides, thereby protecting cells against oxidative damage. Prx I is overexpressed in a range of human cancers. Increased levels have been detected in tumors such as breast, lung, colorectal, liver, pancreatic, and head and neck cancers. In some cases, this upregulation is thought to be a response to the enhanced oxidative stress experienced by rapidly proliferating tumor cells.
1085-	PrxII	↑	Peroxiredoxin II			Prx II is a peroxidase that reduces hydrogen peroxide and organic hydroperoxides. Higher levels of Prx II in cancer cells enhance their ability to detoxify reactive oxygen species (ROS). • This protection against oxidative damage enables tumor cells to survive in a stressful microenvironment characterized by high metabolic activity and inflammation. Prx II is often upregulated in several types of cancers. For example, increased expression of Prx II has been reported in breast, lung, colorectal, and gastric cancers, among others. This upregulation is generally viewed as an adaptive response of cancer cells to the increased oxidative stress associated with rapid proliferation and a hostile tumor microenvironment. -higher Prx II expression has been associated with unfavorable clinical outcomes. • Many cancer therapies, including chemotherapy and radiation therapy, rely on the generation of ROS to induce cancer cell death. Elevated levels of Prx II can reduce the efficacy of these treatments by neutralizing ROS, thereby contributing to resistance.
939-	pS2/TFF1	↓	pS2/TFF1			pS2 (also known as TFF1) is a protein that is involved in various cellular processes, including cell growth, differentiation, and survival. In the context of cancer, pS2 has been implicated in several types of cancer, including breast, ovarian, endometrial, prostate, lung, and colorectal cancer. -Tumor suppressor: pS2 has been shown to have tumor suppressor properties, as it can inhibit cell growth and induce apoptosis (cell death) in cancer cells. -Hormone regulation: pS2 is a progesterone-induced gene, and its expression is regulated by hormonal changes. In cancer, pS2 expression can be influenced by hormonal imbalances, leading to changes in tumor growth and behavior. -Cell adhesion and migration: pS2 has been shown to regulate cell adhesion and migration, which are critical processes in cancer metastasis. -Angiogenesis: pS2 has been implicated in the regulation of angiogenesis, the process of new blood vessel formation, which is essential for tumor growth and metastasis. pS2 is often downregulated in various types of cancer, including breast, ovarian, endometrial, prostate, lung, and colorectal cancer.
264-	PSA	↑	prostate-specific antigen			Prostate-Specific Antigen (PSA) is a protein produced by both normal and malignant cells of the prostate gland. PSA testing is commonly used as a screening tool for prostate cancer. Elevated levels of PSA in the blood can indicate the presence of prostate cancer, but they can also be caused by other conditions, such as benign prostatic hyperplasia (BPH) or prostatitis (inflammation of the prostate).
649-	PSMB5	↑	proteasome subunit beta type-5			PSMB5 is a gene that provides instructions for making a protein called proteasome subunit beta type-5. This protein is a part of the larger proteasome complex, which helps break down unneeded or damaged proteins in the cell. PSMB5 is a key component of the proteasome complex whose altered expression or mutation plays an important role in cancer biology. In hematologic malignancies—especially multiple myeloma—elevated levels or mutant forms of PSMB5 are associated with resistance to proteasome inhibitors and poorer outcomes. In solid tumors, increased proteasome activity via PSMB5 may support tumor cell survival under proteotoxic and metabolic stress, although its prognostic value can be more variable.
266-	PTCH1	↓	12-transmembrane cell surface receptor Patched1	CGL-Driver	TSG Gene	When not bound by Hh ligands, PTCH1 restrains the activity of Smo. The protein functions as a receptor protein for sonic hedgehog, desert hedgehog, and indian hedgehog proteins. PTCH1 (Patched 1) is a gene that plays a crucial role in the Hedgehog signaling pathway, which is important for cell growth, differentiation, and tissue patterning during embryonic development. Mutations in the PTCH1 gene are associated with several types of cancer. PTCH1 and PTCH2 act as tumor suppressors by maintaining control over Hedgehog signaling. Their loss—whether by mutation or reduced expression—leads to unchecked pathway activation, supporting cell proliferation and survival. Such abnormalities are associated with a more aggressive tumor phenotype and poorer clinical outcomes in cancers where the Hedgehog pathway is a driver of tumorigenesis
433-	PTCH2	↓	PTCH2		gene	PTCH2 gene mutations have been found in an inherited condition called basal cell nevus syndrome and in some types of cancer, including basal cell skin cancer and medulloblastoma (a type of brain cancer). PTCH1 and PTCH2 act as tumor suppressors by maintaining control over Hedgehog signaling. Their loss—whether by mutation or reduced expression—leads to unchecked pathway activation, supporting cell proliferation and survival. Such abnormalities are associated with a more aggressive tumor phenotype and poorer clinical outcomes in cancers where the Hedgehog pathway is a driver of tumorigenesis
267-	PTEN	↓	phosphatase and tensin homolog; phosphatase and tensin homolog pseudogene 1	CGL-Driver Genes	TSG	PTEN (Phosphatase and Tensin Homolog) is a crucial tumor suppressor gene that plays a significant role in regulating cell growth, proliferation, and survival. It encodes a protein that functions as a phosphatase, which means it removes phosphate groups from specific molecules, thereby regulating various signaling pathways, particularly the PI3K/AKT pathway. PTEN is mutated, deleted, or otherwise inactivated. This loss of function can lead to increased cell proliferation and survival, contributing to tumorigenesis. PTEN mutations are commonly found in various cancers, including: Prostate cancer Breast cancer Endometrial cancer Glioblastoma
641-	PTP1B	↑	protein tyrosine phosphatase 1B			PTP1B (protein tyrosine phosphatase 1B) is a protein that has been linked to the development and progression of certain types of cancer. It plays a role in regulating insulin signaling, and dysregulation of this pathway can contribute to cancer cell growth and survival. In cancer cells, PTP1B has been shown to promote processes such as epithelial-mesenchymal transition (EMT), which allows cancer cells to become more invasive and metastatic. PTP1B inhibitors have been shown to reduce tumor growth and metastasis in various cancer models. In general, PTP1B expression is upregulated in cancer cells, which can contribute to cancer progression and resistance to therapy.
268-	PTPN11	↑	protein tyrosine phosphatase, non-receptor type 11; similar to protein tyrosine phosphatase, non-receptor type 11	CGL-Driver Genes	Oncogene	PTPN11, also known as SHP-2, is a protein tyrosine phosphatase that plays a crucial role in various cellular processes, including cell growth, differentiation, and survival. It is involved in signaling pathways that are activated by growth factors and cytokines. PTPN11 plays a pivotal role in mediating key growth and survival pathways. In many cancers—notably certain leukemias and subsets of solid tumors—activating mutations or overexpression of PTPN11 contribute to oncogenesis by amplifying downstream signals such as RAS/MAPK and PI3K/AKT. These alterations are generally associated with more aggressive tumor behavior and poorer outcomes, making PTPN11 both a prognostic marker and a target for emerging therapeutic interventions.
923-	PTPN6	↓	SHP1/Protein Tyrosine Phosphatase, Non-Receptor Type 6			also known as SHP-1 (Src Homology 2 Domain-Containing Phosphatase 1) SHP-1 (Src homology 2 domain-containing phosphatase-1) is a protein tyrosine phosphatase that plays a crucial role in regulating various cellular processes, including cell signaling, proliferation, and survival. Its expression has been implicated in the development and progression of various types of cancer. Low SHP-1 expression is associated with poor prognosis, increased tumor size, and lymph node metastasis.
430-	PUMA	↓	p53 upregulated modulator of apoptosis		pro-apoptotic protein	The expression of PUMA is regulated by the tumor suppressor p53. PUMA serves as an important proapoptotic factor that functions as a tumor suppressor by facilitating the elimination of damaged or aberrant cells. In many cancers, impaired induction of PUMA—often due to p53 dysfunction—correlates with treatment resistance and aggressive disease.
1158-	PYCR1	↑	Pyrroline-5-Carboxylate Reductase 1			Pyrroline-5-Carboxylate Reductase 1 (PYCR1) is an enzyme that catalyzes the final step in proline biosynthesis by reducing pyrroline-5-carboxylate to proline. This enzyme plays an integral role in cellular metabolism and redox balance. In the context of cancer, PYCR1 has emerged as a notable factor, with its expression levels often correlating with tumor progression and patient prognosis. -Numerous studies have found that PYCR1 is overexpressed in a variety of tumor types, including breast cancer, lung cancer, liver cancer, and others. Elevated PYCR1 expression is thought to provide tumor cells with a survival advantage by contributing to anabolic metabolism and helping to mitigate oxidative stress.
1138-	Pyro	?	Pyroptosis			Pyroptosis is a form of programmed cell death characterized by the formation of membrane pores by gasdermin proteins, leading to cell swelling, lysis, and the release of inflammatory mediators.
987-	Pyruv	↑	Pyruvate			Pyruvate is a small organic molecule that is a key intermediate in several metabolic pathways. It is the end product of glycolysis, a process that breaks down glucose to release energy. Increased conversion of pyruvate to lactate (via lactate dehydrogenase, LDH) contributes to the acidification of the tumor microenvironment, which can promote tumor invasion and immune evasion. Cancer cells can dynamically adjust pyruvate utilization based on nutrient availability. Under certain conditions, some cancer cells may reroute pyruvate to the mitochondria for oxidative phosphorylation, especially in nutrient- or oxygen-rich environments. This flexibility also means that targeting pyruvate metabolism (e.g., by inhibiting key enzymes like PKM2 or PDKs) is an area of interest in cancer therapy. pyruvate is a central metabolite whose handling in cancer cells is redirected to favor increased glycolysis and lactate production over oxidative phosphorylation. This metabolic reprogramming is a key driver of tumor cell survival, proliferation, and adaptation to stress, and is associated with poor prognosis in multiple cancer types. Although not “expressed” like a protein, the regulation of pyruvate metabolism is clearly protumorigenic by sustaining the energetic and biosynthetic demands of cancer, and is an area of active therapeutic exploration.
1141-	QoL	↓	Quality of Life			Quality of Life
1293-	R5P	↑	ribose-5-phosphate			R5P is a key metabolite in the pentose phosphate pathway (PPP), where it plays a critical role in generating ribonucleotide precursors for RNA and DNA synthesis. The PPP also produces NADPH, which is vital for reductive biosynthesis and protecting cells against oxidative stress. R5P itself is a metabolite rather than a protein or gene product, its levels (or the activity of enzymes that regulate its production) have been associated with tumor biology and outcome in several cancer types. Much of the published data focuses on enzymes such as transketolase, transaldolase, and glucose-6-phosphate dehydrogenase (G6PD), which regulate R5P production. -Elevated PPP activity—reflected in increased production of R5P—has been linked to enhanced cell proliferation, aggressive tumor behavior, and poorer prognosis across several cancer types including breast, lung, colorectal, hepatocellular carcinoma, and potentially gliomas.
879-	Rac1	↑	Ras-related C3 botulinum toxin substrate 1			Rac1 is a small GTPase that plays a crucial role in various cellular processes, including cell growth, migration, and survival. Rac1 is involved in the regulation of cell migration and invasion, which are critical steps in the metastasis of cancer cells. Rac1 has been found to be overexpressed in cancer tissues and cell lines, and its expression has been associated with poor prognosis. Where Low Rac1 expression is found it has been associated with good prognosis and improved overall survival
666-	RAD51	?	RAD51			RAD51 is a protein that plays a crucial role in the repair of DNA double-strand breaks through homologous recombination (HR). It is a key component of the DNA repair machinery and is essential for maintaining genome stability. RAD51 expression has been correlated with other biomarkers of DNA repair and genomic instability, such as BRCA1 and BRCA2. Overexpression: breast, ovarian, prostate, lung Underexpression: CRC, pancreatic, Hepatocellular, RCC, Melanoma, Thyroid
1185-	radioP	↓	RadioProtective			Protect against the damaging effects of radiation therapy
1107-	RadioS	↓	RadioSensitizer			A radiosensitizer is an agent that makes cancer cells more sensitive to the damaging effects of radiation therapy. By using a radiosensitizer, clinicians aim to enhance the effectiveness of radiation treatment by either increasing the damage incurred by tumor cells or by interfering with the cancer cells’ repair mechanisms. This can potentially allow for lower doses of radiation, reduced side effects, or improved treatment outcomes. List of Natural Products with radiosensitizing properties: -Curcumin:modulate NF-κB, STAT3 and has been shown in preclinical studies to enhance the effects of radiation by inhibiting cell survival pathways. -Resveratrol: -EGCG: -Quercetin: -Genistein: -Parthenolide: how radiosensitizers inhibit the thioredoxin (Trx) system in cellular contexts. Notable radiosensitizers, including: -gold nanoparticles (GNPs), -gold triethylphosphine cyanide ([Au(SCN) (PEt3)]), -auranofin, ceria nanoparticles (CONPs), -curcumin and its derivatives, -piperlongamide, -indolequinone derivatives, -micheliolide, -motexafin gadolinium, and -ethane selenide selenidazole derivatives (SeDs)
480-	Raf	↑	RAF kinases			RAF kinases (ARAF, BRAF and CRAF (also known as RAF1)) constitute core components of the RAS-RAF-MEK-ERK signalling cascade (ERK signalling), a pathway that mediates signals from cell surface receptors to the nucleus to regulate cell growth, differentiation and survival. The RAF family of kinases includes key activators of the pro-tumourigenic mitogen-activated protein kinase pathway. Hyperactivation of RAF proteins, particularly BRAF and CRAF, drives tumour progression and drug resistance in many types of cancer.
383-	RAGE	?	Receptor for advanced glycation end-product			RAGE (receptor for advanced glycation end-product) is thought to be associated with metastasis and poor prognosis of various types of cancer.
1183-	RANKL	↑	Receptor Activator of Nuclear Factor κB Ligand			RANKL (Receptor Activator of Nuclear Factor κB Ligand, formally known as TNFSF11) -High expression of RANKL (or increased activity of the RANK pathway) has been linked to a higher tendency for bone metastasis, particularly in certain subtypes (e.g., estrogen receptor–negative cancers). -Activation of this pathway may predict poor outcomes in specific settings, though the direct prognostic significance of RANKL levels still calls for additional clinical validation.
1221-	RANTES	↑	CCL5			RANTES (Regulated on Activation, Normal T Cell Expressed and Secreted), also known as CCL5 • RANTES/CCL5 is a chemokine that plays a central role in recruiting immune cells—such as T cells, eosinophils, and monocytes—to sites of inflammation. • In the tumor microenvironment, RANTES can influence immune cell infiltration, which may either support anti-tumor responses or, conversely, facilitate a pro-tumorigenic inflammatory milieu depending on the context. • RANTES is involved in modulating angiogenesis, cell migration, and the deposition of extracellular matrix components. These processes can affect tumor progression and metastasis. -In several cancer types—including breast, lung, and colorectal cancers—elevated RANTES expression has been associated with more aggressive tumor behavior and, in some instances, poorer prognosis.
1001-	RARα	↑	RARα (NR1B1)			The retinoic acid receptors (RARs) are members of the nuclear receptor superfamily and function as ligand-activated transcription factors. Three main isoforms have been characterized: • RARα (NR1B1) • RARβ (NR1B2) • RARγ (NR1B3) They bind retinoic acid (the active metabolite of vitamin A) and regulate gene expression programs involved in cell differentiation, proliferation, and apoptosis. RARα is often found to be ubiquitously expressed at baseline in many tissues. In solid tumors, aberrant RARα expression has been observed, but its prognostic role can be variable—sometimes correlating with a more aggressive phenotype if the downstream signaling is disrupted.
1002-	RARβ	↓	RARβ (NR1B2)			The retinoic acid receptors (RARs) are members of the nuclear receptor superfamily and function as ligand-activated transcription factors. Three main isoforms have been characterized: • RARα (NR1B1) • RARβ (NR1B2) • RARγ (NR1B3) They bind retinoic acid (the active metabolite of vitamin A) and regulate gene expression programs involved in cell differentiation, proliferation, and apoptosis. RARβ is frequently found to be downregulated or silenced (often by promoter hypermethylation) in several cancers, including lung, breast, and prostate cancers. • Its loss is thought to contribute to tumor progression by diminishing the retinoid-induced differentiation and apoptosis signals. Decreased RARβ expression is often associated with a poorer prognosis.
1003-	RARγ	↑	RARγ (NR1B3)			The retinoic acid receptors (RARs) are members of the nuclear receptor superfamily and function as ligand-activated transcription factors. Three main isoforms have been characterized: • RARα (NR1B1) • RARβ (NR1B2) • RARγ (NR1B3) They bind retinoic acid (the active metabolite of vitamin A) and regulate gene expression programs involved in cell differentiation, proliferation, and apoptosis. In certain cancers (such as colon cancer, prostate cancer, and some hematologic malignancies), RARγ may be preferentially expressed or even overexpressed, potentially supporting cancer cell survival and proliferation. Elevated RARγ expression in some tumor types has been linked with a poorer prognosis. • In prostate and colon cancer, increased RARγ signaling may contribute to sustained proliferation and resistance to apoptosis.
269-	RAS	↑	RAS	CGL-CS		family of RAS proteins (KRAS, NRAS, and HRAS) have been well described to cause oncogenic transformation - the expression and mutational status of RAS isoforms are critical in several cancers and are generally linked with a poorer prognosis when mutated
270-	RB1	↓	retinoblastoma 1 gene	CGL-Driver Genes	TSG	The RB1 gene is a critical tumor suppressor gene that plays a significant role in regulating the cell cycle, thereby preventing uncontrolled cell growth and tumor formation. The RB1 gene encodes the retinoblastoma protein (pRB), which helps control the cell cycle by regulating the transition from the G1 (gap 1) phase to the S (synthesis) phase. When functioning properly, pRB binds to and inhibits transcription factors that promote cell division. The loss of RB1 function is often associated with a more aggressive tumor phenotype and poorer clinical outcomes.
1242-	RBM3	↓	RNA-binding motif protein 3		biomarker	RBM3 (RNA-binding motif protein 3) is a cold-shock protein that has garnered interest due to its involvement in RNA metabolism, stress response, and potentially tumor biology Overall, elevated RBM3 expression tends to correlate with improved prognosis in several cancers, including breast, colorectal, ovarian, and prostate cancers, among others. Its consistent association with better outcomes has highlighted RBM3 as a promising prognostic biomarker
271-	RECK	↓	Reversion Inducing Cysteine-Rich Protein with Kazal Motifs			RECK (Reversion Inducing Cysteine-Rich Protein with Kazal Motifs) is a protein that has been studied for its role in cancer biology. It is known to function as a tumor suppressor and is involved in the regulation of extracellular matrix remodeling, cell adhesion, and migration. RECK is generally considered a tumor suppressor. Its expression is often downregulated in various cancers, which can contribute to tumor progression, invasion, and metastasis.
588-	REL	↑	V-rel avian reticuloendotheliosis viral oncogene homolog (REL)			REL, is a protein that plays a crucial role in the regulation of cell growth, differentiation, and survival. REL is a member of the NF-κB family of transcription factors, which are involved in various cellular processes, including immune responses, inflammation, and cell proliferation. REL has been implicated in the development and progression of various types of cancer, including lymphomas, leukemias, and solid tumors. The protein is often constitutively active in cancer cells, leading to the activation of genes involved in cell proliferation, survival, and angiogenesis. Studies have shown that REL is overexpressed in several types of cancer. REL can also interact with other transcription factors, such as p50 and p65, to form heterodimers that regulate gene expression. -Activation of cell cycle progression: REL can activate genes involved in cell cycle progression, leading to increased cell proliferation. -Inhibition of apoptosis: REL can inhibit apoptosis by activating anti-apoptotic genes and repressing pro-apoptotic genes. -Promotion of angiogenesis: REL can activate genes involved in angiogenesis, leading to increased blood vessel formation and tumor growth. -Modulation of immune responses: REL can modulate immune responses by regulating the expression of genes involved in inflammation and immune cell activation.
810-	Remission	?	Remission		target
1175-	RenoP	↓	Renoprotection			protects kidneys -same as nephroprotective Opposite is : Nephrotoxicity is toxicity in the kidneys
272-	RET	?	Rearranged during Transfection proto-oncogene	CGL-Driver Genes	Oncogene	RET (Rearranged during Transfection) is a gene that encodes a receptor tyrosine kinase, which plays a crucial role in cell signaling, particularly in the development of the nervous system and the regulation of various cellular processes.
817-	RHBDD1	↑	Rhomboid Domain Containing 1			RHBDD1 encodes a member of the rhomboid family of intramembrane serine proteases. Although the precise functions of RHBDD1 are still being elucidated, emerging evidence suggests that it may influence several cancer-related processes including cell proliferation, apoptosis, and migration. Its enzymatic role within the cell, particularly in the modulation of signaling pathways through regulated proteolysis, is thought to contribute to changes in the tumor microenvironment and tumor progression. In certain cancer types—such as colorectal, hepatocellular, or breast cancers—RHBDD1 expression has been found to be upregulated. The increased expression of RHBDD1 in tumors suggests that it may contribute to oncogenic transformation or progression Higher levels of RHBDD1 expression have been associated with increased tumor proliferation and poorer survival rates in some cancers. RHBDD1 holds promise both as a prognostic biomarker and as a potential therapeutic target.
273-	Rho	?	Rho GTPases			The Rho GTPases RhoA, Rac1, and Cdc42 are important regulators of cytoskeletal dynamics. small GTPase Ras homolog gene family member A (RHOA) RHOA: Ras homolog family member A many in vitro and in vivo data indicate tumor-promoting effects of activated Rho GTPases, also tumor suppressive functions have been described In many cancers, RhoA and RhoC are often found to be overexpressed. RhoB expression can be downregulated in certain cancers, which may contribute to tumor progression. Unlike RhoA and RhoC, RhoB is often considered a tumor suppressor, and its loss can lead to increased cell proliferation and survival.
942-	RIP1	↑	Receptor-Interacting Protein 1			RIP1 (Receptor-Interacting Protein 1) is a protein kinase that plays a crucial role in cell signaling pathways, including those involved in inflammation, cell death, and cancer. RIP1 is often overexpressed, and associated with poor prognosis RIP1 and RIP3 are key regulators of necroptosis and are involved in intricate signaling pathways that dictate cell survival, inflammation, and death. Their dual roles in cancer can have opposing effects on tumor progression: while necroptosis may promote anti-tumor immunity and improve outcomes in some contexts, pro-survival signaling mediated by RIP1 can contribute to tumor aggressiveness and resistance to therapy.
1066-	RIP3	↓	Receptor‐Interacting Protein Kinase 3			RIP3 Receptor‐Interacting Protein Kinase 3 Several cancers have decreased RIP3 expression and is associated with poorer prognosis, more aggressive tumor behavior, and resistance to chemotherapies. Restoration of RIP3 may promote necroptosis, providing a potential mechanism to overcome therapy resistance.
785-	Risk	?	Risk
274-	RNF43	?	ring finger protein 43	CGL-Driver Genes	TSG	RNF43 (Ring Finger Protein 43) is a gene that encodes a protein involved in various cellular processes, including the regulation of Wnt signaling, which is crucial for cell proliferation, differentiation, and development. RNF43 is considered a potential tumor suppressor gene, and its loss of function may lead to increased cancer cell proliferation.
821-	RNR	↑	Ribonucleotide Reductase		enzyme	RNR (Ribonucleotide Reductase) is an enzyme that plays a crucial role in the synthesis of DNA. It is responsible for converting ribonucleotides into deoxyribonucleotides, which are the building blocks of DNA. In cancer, RNR is often overexpressed, which can contribute to the rapid growth and proliferation of cancer cells. This is because cancer cells require a constant supply of DNA building blocks to support their rapid division. Research has shown that inhibiting RNR can be an effective way to slow down or stop the growth of cancer cells.
276-	RNS	?	reactive nitrogen species			Reactive nitrogen species (RNS) are chemically reactive molecules that contain nitrogen and can play significant roles in cellular signaling and homeostasis. Like reactive oxygen species (ROS), RNS can have both beneficial and detrimental effects in the context of cancer.
1284-	ROCK1	↑	Rho-associated coiled-coil containing protein kinase 1			ROCK1 (Rho-associated coiled-coil containing protein kinase 1) – ROCK1 is a serine/threonine kinase and a major effector of the Rho GTPase signaling pathway. – Elevated expression of ROCK1 has been observed in various cancers, including breast, prostate, lung, colorectal, and gastric cancers. – In many tumors, ROCK1 overexpression correlates with increased cell motility, invasion, and metastatic potential.
569-	ROMO1	?	Reactive Oxygen Species Modulator 1			One of the most important proteins in the inner membrane of mitochondria is Reactive Oxygen Species (ROS) Modulator 1 (ROMO1) that interferes with the production of ROS, and with increasing the rate of this protein, oxidative stress will increase, which ultimately leads to some diseases, especially cancer.
275-	ROS	?	Reactive Oxygen Species	HalifaxProj (inhibit)		Reactive oxygen species (ROS) are highly reactive molecules that contain oxygen and can lead to oxidative stress in cells. They play a dual role in cancer biology, acting as both promoters and suppressors of cancer. ROS can cause oxidative damage to DNA, leading to mutations that may contribute to cancer initiation and progression. So normally you want to inhibit ROS to prevent cell mutations. However excessive ROS can induce apoptosis (programmed cell death) in cancer cells, potentially limiting tumor growth. Chemotherapy typically raises ROS. "Reactive oxygen species (ROS) are two electron reduction products of oxygen, including superoxide anion, hydrogen peroxide, hydroxyl radical, lipid peroxides, protein peroxides and peroxides formed in nucleic acids 1. They are maintained in a dynamic balance by a series of reduction-oxidation (redox) reactions in biological systems and act as signaling molecules to drive cellular regulatory pathways." "During different stages of cancer formation, abnormal ROS levels play paradoxical roles in cell growth and death 8. A physiological concentration of ROS that maintained in equilibrium is necessary for normal cell survival. Ectopic ROS accumulation promotes cell proliferation and consequently induces malignant transformation of normal cells by initiating pathological conversion of physiological signaling networks. Excessive ROS levels lead to cell death by damaging cellular components, including proteins, lipid bilayers, and chromosomes. Therefore, both scavenging abnormally elevated ROS to prevent early neoplasia and facilitating ROS production to specifically kill cancer cells are promising anticancer therapeutic strategies, in spite of their contradictoriness and complexity." "ROS are the collection of derivatives of molecular oxygen that occur in biology, which can be categorized into two types, free radicals and non-radical species. The non-radical species are hydrogen peroxide (H 2O 2 ), organic hydroperoxides (ROOH), singlet molecular oxygen ( 1 O 2 ), electronically excited carbonyl, ozone (O3 ), hypochlorous acid (HOCl, and hypobromous acid HOBr). Free radical species are super-oxide anion radical (O 2•−), hydroxyl radical (•OH), peroxyl radical (ROO•) and alkoxyl radical (RO•) [130]. Any imbalance of ROS can lead to adverse effects. H2 O 2 and O 2 •− are the main redox signalling agents. The cellular concentration of H2 O 2 is about 10−8 M, which is almost a thousand times more than that of O2 •−". "Radicals are molecules with an odd number of electrons in the outer shell [393,394]. A pair of radicals can be formed by breaking a chemical bond or electron transfer between two molecules." Recent investigations have documented that polyphenols with good antioxidant activity may exhibit pro-oxidant activity in the presence of copper ions, which can induce apoptosis in various cancer cell lines but not in normal cells. https://pubmed.ncbi.nlm.nih.gov/24123728/ "We have shown that such cell growth inhibition by polyphenols in cancer cells is reversed by copper-specific sequestering agent neocuproine to a significant extent whereas iron and zinc chelators are relatively ineffective, thus confirming the role of endogenous copper in the cytotoxic action of polyphenols against cancer cells. Therefore, this mechanism of mobilization of endogenous copper ions could be one of the important mechanisms for the cytotoxic action of plant polyphenols against cancer cells and is possibly a common mechanism for all plant polyphenols. In fact, similar results obtained with four different polyphenolic compounds in this study, namely apigenin, luteolin, EGCG, and resveratrol, strengthen this idea. Interestingly, the normal breast epithelial MCF10A cells have earlier been shown to possess no detectable copper as opposed to breast cancer cells [24], which may explain their resistance to polyphenols apigenin- and luteolin-induced growth inhibition as observed here (Fig. 1). We have earlier proposed [25] that this preferential cytotoxicity of plant polyphenols toward cancer cells is explained by the observation made several years earlier, which showed that copper levels in cancer cells are significantly elevated in various malignancies. Thus, because of higher intracellular copper levels in cancer cells, it may be predicted that the cytotoxic concentrations of polyphenols required would be lower in these cells as compared to normal cells. " majority of ROS are produced as a by-product of oxidative phosphorylation, high levels of ROS are detected in almost all cancers -It is well established that during ER stress, cytosolic calcium released from the ER is taken up by the mitochondrion to stimulate ROS overgeneration and the release of cytochrome c, both of which lead to apoptosis Note: Products that may raise ROS can be found using this database, by: Filtering on the target of ROS, and selecting the Effect Direction of ↑ Targets to raise ROS (to kill cancer cells): • NADPH oxidases (NOX): NOX enzymes are involved in the production of ROS. -Targeting NOX enzymes can increase ROS levels and induce cancer cell death. -eNOX2 inhibition leads to a high NADH/NAD⁺ ratio which can lead to increased ROS • Mitochondrial complex I: Inhibiting can increase ROS production • P53: Activating p53 can increase ROS levels(by inducing the expression of pro-oxidant genes) • Nrf2: regulates the expression of antioxidant genes. Inhibiting Nrf2 can increase ROS levels • Glutathione (GSH): an antioxidant. Depleting GSH can increase ROS levels • Catalase: Catalase converts H2O2 into H2O+O. Inhibiting catalase can increase ROS levels • SOD1: converts superoxide into hydrogen peroxide. Inhibiting SOD1 can increase ROS levels • PI3K/AKT pathway: regulates cell survival and metabolism. Inhibiting can increase ROS levels • HIF-1α: regulates genes involved in metabolism and angiogenesis. Inhibiting HIF-1α can increase ROS • Glycolysis: Inhibiting glycolysis can increase ROS levels • Fatty acid oxidation: Cancer cells often rely on fatty acid oxidation for energy production. -Inhibiting fatty acid oxidation can increase ROS levels • ER stress: Endoplasmic reticulum (ER) stress can increase ROS levels • Autophagy: process by which cells recycle damaged organelles and proteins. -Inhibiting autophagy can increase ROS levels and induce cancer cell death. • KEAP1/Nrf2 pathway: regulates the expression of antioxidant genes. -Inhibiting KEAP1 or activating Nrf2 can increase ROS levels and induce cancer cell death. • DJ-1: regulates the expression of antioxidant genes. Inhibiting DJ-1 can increase ROS levels • PARK2: regulates the expression of antioxidant genes. Inhibiting PARK2 can increase ROS levels • SIRT1:regulates the expression of antioxidant genes. Inhibiting SIRT1 can increase ROS levels • AMPK: regulates energy metabolism and can increase ROS levels when activated. • mTOR: regulates cell growth and metabolism. Inhibiting mTOR can increase ROS levels • HSP90: regulates protein folding and can increase ROS levels when inhibited. • Proteasome: degrades damaged proteins. Inhibiting the proteasome can increase ROS levels • Lipid peroxidation: a process by which lipids are oxidized, leading to the production of ROS. -Increasing lipid peroxidation can increase ROS levels • Ferroptosis: form of cell death that is regulated by iron and lipid peroxidation. -Increasing ferroptosis can increase ROS levels • Mitochondrial permeability transition pore (mPTP): regulates mitochondrial permeability. -Opening the mPTP can increase ROS levels • BCL-2 family proteins: regulate apoptosis and can increase ROS levels when inhibited. • Caspase-independent cell death: a form of cell death that is regulated by ROS. -Increasing caspase-independent cell death can increase ROS levels • DNA damage response: regulates the repair of DNA damage. Increasing DNA damage can increase ROS • Epigenetic regulation: process by which gene expression is regulated. -Increasing epigenetic regulation can increase ROS levels -PKM2, but not PKM1, can be inhibited by direct oxidation of cysteine 358 as an adaptive response to increased intracellular reactive oxygen species (ROS) ProOxidant Strategy:(inhibit the Melavonate Pathway (likely will also inhibit GPx) -HydroxyCitrate (HCA) found as supplement online and typically used in a dose of about 1.5g/day or more -Atorvastatin typically 40-80mg/day -Dipyridamole typically 200mg 2x/day -Lycopene typically 100mg/day range https://pmc.ncbi.nlm.nih.gov/articles/PMC8364652/ Dual Role of Reactive Oxygen Species and their Application in Cancer Therapy
762-	RPM	?	radical pair mechanism			The radical pair mechanism is a process that involves the interaction of two radicals (highly reactive molecules with unpaired electrons) and has been found to be sensitive to magnetic fields. In the presence of a magnetic field, the radical pair mechanism can be influenced, leading to changes in the reaction rates and yields. The magnetic field effect on radical pair reactions can be explained by the following mechanisms: Spin-correlated radical pairs: In the presence of a magnetic field, the spin-correlated radical pairs can be formed, which can lead to changes in the reaction rates and yields. Spin relaxation: The magnetic field can influence the spin relaxation of the radicals, leading to changes in the reaction rates and yields. Magnetic field-induced intersystem crossing: The magnetic field can induce intersystem crossing between the singlet and triplet states, leading to changes in the reaction rates and yields.
715-	RPS6KA1	↑	ribosomal protein S6 kinase alpha-1		gene	RPS6KA1 is a gene that encodes a protein called ribosomal protein S6 kinase alpha-1. This protein is involved in various cellular processes, including cell growth, proliferation, and survival. Research has shown that RPS6KA1 is overexpressed in several types of cancer, including breast, lung, and colon cancer.
830-	RPSA	↑	Ribosomal Protein SA			also known as 67LR RPSA and 67LR have been shown to be identical proteins, with RPSA being a cytoplasmic protein and 67LR being a cell surface receptor. Ribosomal Protein SA (RPSA) is a protein that plays a crucial role in the translation of genetic information into proteins. It is a component of the 40S subunit of the ribosome, which is responsible for reading messenger RNA (mRNA) and assembling amino acids into proteins. RPSA is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. This overexpression has been linked to cancer progression, metastasis, and poor patient outcomes.
799-	RSK	↑	Ribosomal S6 Kinase			RSK (Ribosomal S6 Kinase) is a family of serine/threonine kinases that play a crucial role in various cellular processes, including cell growth, differentiation, and survival. RSK is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. RSK phosphorylates and activates downstream targets, such as: ERK1/2: promotes cell growth and survival. AKT: promotes cell survival and inhibits apoptosis. NF-κB: promotes cell survival and inflammation. RSK proteins are activated by phosphorylation, which allows them to bind to and phosphorylate downstream targets.
277-	RTK-RAS	↑		TCGA		dysregulation of RTK-RAS signaling is a key driver of tumorigenesis. Overexpression or mutation of RTKs can lead to aberrant activation of RAS, contributing to cancer development. Due to their central role in cancer, both RTKs and RAS proteins are important targets for cancer therapies. Inhibitors targeting RTKs (e.g., EGFR inhibitors) and RAS (e.g., direct RAS inhibitors) are being developed and tested in clinical settings.
278-	RUNX1	?	runt-related transcription factor 1	CGL-Driver Genes	TSG	RUNX1 is a gene that encodes a transcription factor involved in the regulation of hematopoiesis (the formation of blood cells) and is crucial for the development of various blood cell lineages. It plays a significant role in the differentiation and function of hematopoietic stem cells. RUNX1 is often considered a tumor suppressor in hematopoietic cells. Loss of RUNX1 function can lead to uncontrolled cell proliferation and survival, contributing to cancer progression.
776-	RUNX2	↑	Runt-related transcription factor 2			RUNX2 (Runt-related transcription factor 2) is a transcription factor that plays a crucial role in the regulation of bone development and osteoblast differentiation. RUNX2 is overexpressed in: breast, prostate, lung, osteosarcoma.
735-	S6	↑	ribosomal protein S6			S6, also known as ribosomal protein S6, is a protein that plays a crucial role in the regulation of cell growth and proliferation. Research has shown that S6 is involved in various cellular processes, including protein synthesis, cell cycle progression, and apoptosis. Elevated levels of S6 have been observed in many types of cancer, including breast, lung, and colon cancer. S6 is a downstream target of the mTOR (mechanistic target of rapamycin) signaling pathway, which is a key regulator of cell growth and metabolism. Activation of the mTOR pathway can lead to increased S6 activity, which can promote cancer cell growth and survival.
704-	S6K	↑	S6 kinase		protein	S6K (S6 kinase) is a protein that plays a crucial role in cell growth, proliferation, and survival. It is a downstream target of the mTOR (mechanistic target of rapamycin) signaling pathway, which is a central regulator of cellular metabolism, growth, and division. Research has shown that S6K is involved in the development and progression of various types of cancer, including breast, lung, prostate, and colon cancer. Overexpression or hyperactivation of S6K has been observed in many cancer types
859-	SA	↑	Sialic acid			Sialic acid (SA) is a type of sugar molecule that plays a crucial role in various biological processes, including cell-to-cell interactions, immune responses, and cancer progression. Sialic acid (SA) is overexpressed on the surface of tumor cells
297-	SA of VW	?	Structural abnormalities of vessel walls	HalifaxProj(inhibit)		Structural abnormalities in vessel walls can include changes in the composition and organization of the extracellular matrix, alterations in smooth muscle cell function, and endothelial dysfunction. These changes can contribute to the weakening of blood vessels, increased stiffness, and the formation of plaques, which can ultimately lead to cardiovascular events like heart attacks and strokes
849-	SAM-e	⇅	S-adenosylmethionine			S-adenosylmethionine (SAM-e) is a naturally occurring compound that plays a crucial role in various cellular processes, including methylation, gene expression, and cell growth. SAM-e has been studied for its potential anti-cancer effects, and some research suggests that it may have a role in cancer prevention and treatment. Properties: -Inhibition of cancer cell growth -Induction of apoptosis -Inhibition of angiogenesis -Modulation of epigenetic marks: SAM-e is involved in the regulation of epigenetic marks, such as DNA methylation and histone modification -Antioxidant and anti-inflammatory effects SAM-e expression decreased in: Liver, Breast, CRC, prostate, GC, ESo, Pancreatic SAM-e expressing is increased in: Lung, Pancreatic, Ovarian, Melanoma, Thyroid, Renal GBM
494-	SAPK	?	stress-activated protein kinases			SAPK relay, amplify and integrate signals, mainly associated with cellular stress, to allow cell adaptation. p53 and the SAPK pathways are frequently co-compromized in human cancer cells
964-	SAT1	↑	Spermidine/Spermine N1-Acetyltransferase 1			The SAT1 gene (Spermidine/Spermine N1-Acetyltransferase 1) is a key regulator of polyamine metabolism, particularly in the regulation of spermidine and spermine levels. The SAT1 gene is overexpressed in various types of cancer. AT1 gene is a key regulator of polyamine metabolism and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.
958-	SCD1	↑	Stearoyl-CoA Desaturase 1			Stearoyl-CoA Desaturase 1 (SCD1) is an enzyme that plays a crucial role in the regulation of fatty acid metabolism, particularly in the synthesis of monounsaturated fatty acids. lipid synthesis gene SCD1 is overexpressed and is associated with poor prognosis and reduced overall survival in breast, lung, and colon cancers. -SCD1 expression is also associated with increased risk of metastasis and recurrence in various types of cancer.
436-	SCF	?	Stem Cell Factor			important role in hematopoiesis (formation of blood cells), spermatogenesis, and melanogenesis. A cytokine that specifically binds the tyrosine kinase receptor c-KIT.
1236-	SD	?	Stable Disease
1037-	SDC1	↓	Syndecan-1 (SDC-1)			Syndecan-1 (SDC-1), a transmembrane heparan sulfate proteoglycan, supports the integrity of the epithelial compartment. Syndecan-1 is a transmembrane heparan sulfate proteoglycan that functions as a coreceptor in cell–matrix and cell–cell interactions. It plays a key role in modulating signaling pathways through its extracellular domain, which interacts with growth factors, cytokines, and components of the extracellular matrix. Through these interactions, Syndecan-1 influences critical cellular processes such as adhesion, proliferation, migration, and differentiation. the expression of Syndecan-1 is often deregulated. However, its expression can be either upregulated or downregulated depending on the tumor type and its stage of progression. For example, high levels of Syndecan-1 are observed in multiple myeloma, while in other cancers, such as certain carcinomas, loss or redistribution from the cell membrane to the cytoplasm is linked with tumor progression.
531-	SDH	?	Succinate dehydrogenase/ComplexII			Succinate dehydrogenase (Complex II) plays a dual role in respiration by catalyzing the oxidation of succinate to fumarate in the mitochondrial Krebs cycle and transferring electrons from succinate to ubiquinone in the mitochondrial electron transport chain (ETC).
683-	SE-cad	?	Selenocysteine-containing enzyme glutathione peroxidase 1 (GPx1)		enzyme	SE-cad, also known as Selenocysteine-containing enzyme glutathione peroxidase 1 (GPx1), is an enzyme that plays a crucial role in protecting cells from oxidative damage. SE-cad has been found to have both tumor-suppressing and tumor-promoting effects, depending on the type of cancer and the cellular context.
1110-	selectivity	∅	selectivity			The selectivity of cancer products (such as chemotherapeutic agents, targeted therapies, immunotherapies, and novel cancer drugs) refers to their ability to affect cancer cells preferentially over normal, healthy cells. High selectivity is important because it can lead to better patient outcomes by reducing side effects and minimizing damage to normal tissues. Achieving high selectivity in cancer treatment is crucial for improving patient outcomes. It relies on pinpointing molecular differences between cancerous and normal cells, designing drugs or delivery systems that exploit these differences, and overcoming intrinsic challenges like tumor heterogeneity and resistance Factors that affect selectivity: 1 Ability of Cancer cells to preferentially absorb a product/drug -EPR-enhanced permeability and retention of cancer cells -nanoparticle formations/carriers may target cancer cells over normal cells -Liposomal formations. Also negatively/positively charged affects absorbtion 2.product/drug effect may be different for normal vs cancer cells - hypoxia - transition metal content levels (iron/copper) change probability of fenton reaction. - pH levels - antiOxidant levels and defense levels 3.Bio-availability
1172-	selenoP	⇅	selenoproteins			Selenoproteins are a group of proteins that incorporate the rare amino acid selenocysteine into their structure. Selenocysteine, sometimes called the “21st amino acid,” is encoded by the UGA codon in a unique context that requires specific translational machinery. Many selenoproteins are known for their antioxidant and redox-regulatory functions, which are critical in maintaining cellular homeostasis. These functions help protect cells from oxidative stress and damage—processes that, when dysregulated, can contribute to carcinogenesis. Roles of Selenoproteins in Cancer 1. Antioxidant Defense & Redox Regulation -Glutathione Peroxidases (GPxs): Enzymes like GPX1, GPX2, and GPX3 reduce hydrogen peroxide and lipid hydroperoxides. This protects cells against oxidative DNA damage. -Thioredoxin Reductases (TXNRDs): TXNRD1, TXNRD2, and TXNRD3 help maintain the reduced state of thioredoxin, thereby contributing to redox homeostasis and cell survival under stress. 2.Cellular Proliferation and Apoptosis -Selenoproteins may modulate signaling pathways that regulate cell cycle progression and apoptosis. Variations in expression levels—either upregulation or downregulation—can tip the balance toward uncontrolled cell growth or cell death. The expression of selenoproteins in cancers is complex and can vary by tumor type. Here are some examples: Glutathione Peroxidases (GPxs) -GPX1: Both overexpression and underexpression have been reported depending on the tumor context. In some cases, high GPX1 expression can help cancer cells survive oxidative stress -GPX2: Often upregulated in colorectal cancer and some GC, poor prognosis -GPX3: Typically downregulated in many cancers with tumor progression and poor outcome, suggesting its role as a tumor suppressor. Thioredoxin Reductases (TXNRDs) -TXNRD1: Frequently overexpressed in various tumors such as lung, breast, and liver cancers. High TXNRD1 levels are generally associated with a poor prognosis. -SELENOP (Selenoprotein P) SELENOP serves as a selenium transport protein and has antioxidant properties. Decreased SELENOP expression has been linked to poorer outcomes in some cancers, possibly due to reduced selenium availability for other protective selenoproteins. Other Selenoproteins -SELENOF and SELENOS: -SELENOM and SELENOK:
1173-	selm	↓	selenium			Colorectal cancer patients had significantly lower serum selenium concentration than the comparison patients (67.24±15.55 μg/L vs 78.81±12.93 μg/L; P<0.001), and selenium concentration was below the reference range in a high percentage of colorectal cancer patients. https://pmc.ncbi.nlm.nih.gov/articles/PMC10962284/
854-	Sema3A/PlexinA1	⇅	Sema3A/PlexinA1			Sema3A and its receptor, PlexinA1 (PlxnA1), have been implicated in various types of cancer. Sema3A (Semaphorin 3A) is a member of the semaphorin family of proteins, which play a crucial role in regulating cell signaling, migration, and adhesion.
1264-	Sepsis	↑	Sepsis			Sepsis is a life-threatening medical condition that occurs when the body’s response to an infection causes widespread inflammation. This uncontrolled inflammatory response can lead to tissue damage, organ failure, and, in severe cases, death. -treatment options PKM2, Glycolysis and HIF1α inhibitors -Chemotherapy, radiation therapy, and immunosuppressive drugs can further weaken the immune system, making patients more susceptible to infections that can lead to sepsis. -AgNPs have demonstrated antimicrobial effects against a wide range of pathogens including bacteria, fungi, and viruses. Since infections are the primary trigger for sepsis, their ability to reduce microbial loads has been of significant interest
850-	serineP	↑	serine protease			Serine proteases are a family of enzymes that play a crucial role in various cellular processes, including cell growth, differentiation, and survival. Role of serine proteases in cancer: -Tumor growth and angiogenesis: Serine proteases, such as urokinase-type plasminogen activator (uPA) and plasminogen activator inhibitor-1 (PAI-1), are involved in the regulation of tumor growth and angiogenesis. -Invasion and metastasis: Serine proteases, such as (MMPs) and cathepsins, are involved in the degradation of the extracellular matrix, facilitating tumor cell invasion and metastasis.
919-	SESN2	↓	Sestrin 2			Sestrin 2 (SESN2) is a protein that plays a crucial role in regulating cellular metabolism, stress response, and apoptosis. High SESN2 expression is associated with better prognosis, including increased overall survival and reduced recurrence. Low SESN2 expression is associated with poor prognosis, including increased tumor size, stage, and metastasis.
1082-	Set9	⇅	SETD7 (SET domain containing lysine methyltransferase 7)			Set9, also known as SETD7 (SET domain containing lysine methyltransferase 7), is an enzyme that mediates the methylation of lysine residues on both histone and non-histone proteins. SETD7 (Set9) is a lysine methyltransferase with complex roles in cancer, affecting both histone and non-histone proteins. Its expression can influence key pathways related to cell cycle control, apoptosis, and inflammation. The prognostic implications of SETD7 expression in cancers are nuanced—while in some instances it supports tumor-suppressive mechanisms (e.g., via p53 activation), in others it may promote tumor progression through alternative signaling pathways, such as those mediated by NF-κB.
279-	SETBP1	?	SET binding protein 1	CGL-Driver Genes	Oncogene	SETBP1 (SET binding protein 1) is a gene that encodes a protein involved in various cellular processes, including transcription regulation and cell signaling. Mutations in the SETBP1 gene have been associated with several types of cancer, particularly hematological malignancies. In some cancers, particularly certain hematological malignancies like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), SETBP1 may be overexpressed.
280-	SETD2	?	SET domain containing 2	CGL-Driver Genes	TSG	SETD2 (SET domain containing 2) is a gene that encodes a protein involved in the regulation of gene expression and chromatin remodeling. It is a histone methyltransferase that specifically trimethylates histone H3 at lysine 36 (H3K36me3), a modification associated with active transcription and DNA damage repair.
281-	SF3B1	?	splicing factor 3b, subunit 1, 155kDa	CGL-Driver Genes	Oncogene	SF3B1 (splicing factor 3b subunit 1) is a gene that encodes a protein involved in the splicing of pre-mRNA, a critical process in gene expression. Mutations in the SF3B1 gene have been associated with various types of cancer, particularly hematological malignancies such as myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML).
869-	sFasL	↑	soluble Fas Ligand			sFasL (soluble Fas Ligand) is a protein that plays a crucial role in the regulation of apoptosis (programmed cell death) and immune responses. sFasL has been shown to promote tumor growth, invasion, and metastasis by regulating the expression of genes involved in cell proliferation, survival, and migration. sFasL has been found to be highly expressed in cancer stem cells
745-	SFRP5	↓	Secreted Frizzled-Related Protein 5		tumor suppressor protein	SFRP5 (Secreted Frizzled-Related Protein 5) is a member of the SFRP family of proteins, which are known to play a role in regulating the Wnt signaling pathway. SFRP5 has been found to act as a tumor suppressor. It inhibits the Wnt/β-catenin signaling pathway, which is often aberrantly activated in various types of cancer, including colorectal, breast, and lung cancers. SFRP5 expression is frequently downregulated or lost in cancer cells
1200-	SGLTs	↑	Sodium-Glucose Cotransporters			Sodium-Glucose Cotransporters (SGLTs) primarily functions in the uptake of glucose in a sodium-dependent manner—distinct from the facilitative glucose transporters (GLUTs) • SGLTs (notably SGLT1 and SGLT2) facilitate active glucose uptake, which is especially important in tissues where glucose levels are low or where rapid uptake is needed. – Some studies have observed overexpression of SGLT1 in certain tumor types, including pancreatic, prostate, and colorectal cancers. – SGLT1 expression in tumors may correlate with aggressive growth behavior as it supports increased glucose uptake in environments where GLUT activity might be insufficient.
992-	SHARP	⇅	SHARP1/BHLHE41			SHARP1/BHLHE41 is a basic helix-loop-helix (bHLH) transcription factor that regulates gene expression by binding to E-box elements in target gene promoters. -a suppressor of breast cancer metastasis – It generally functions as a transcriptional repressor, controlling the expression of genes involved in circadian rhythm, differentiation, and metabolism. • Circadian Rhythm and Metabolism: – SHARP1 plays a role in maintaining circadian rhythm by modulating the oscillatory expression of clock genes. – Through these regulatory networks, it also influences energy metabolism and cell-cycle control. – Some studies report downregulation of SHARP1 in certain cancers, which may correlate with loss of its differentiation and growth-suppressive functions. – In other contexts, SHARP1 may be upregulated, potentially reflecting an adaptive response to the altered microenvironment or a compromised circadian program in tumors.
805-	Sharpin	↑	SHANK-associated RH domain interactor			SHARPIN (SHANK-associated RH domain interactor) is a protein that plays a crucial role in the regulation of cell growth, survival, and migration. SHARPIN is involved in the regulation of cell growth and survival, and its overexpression has been linked to the development of cancer.
881-	SHBG	↑	Sex Hormone-Binding Globulin			SHBG (Sex Hormone-Binding Globulin) is a protein that binds to sex hormones, such as testosterone and estrogen, and regulates their activity in the body. SHBG can modulate the expression of hormone receptors, such as androgen receptors and estrogen receptors, which are involved in the growth and development of cancer cells. High SHBG expression has been associated with poor prognosis and reduced overall survival in cancer patients. Low SHBG expression has been associated with good prognosis and improved overall survival in cancer patients.
431-	Shc	?	Shc signaling proteins			implicated in many pathways associated with aggressive disease, and many breast cancer cell lines derived from highly aggressive tumors contain high levels of activated, tyrosine phosphorylated (PY)-Shc
282-	Shh	↑	sonic hedgehog		Hedgehog	components of Shh pathway (smoothened, patched, Gli1 and Gli2) Sonic Hedgehog (SHH) is a key signaling protein involved in various developmental processes, including cell growth, differentiation, and tissue patterning. The SHH signaling pathway is crucial during embryonic development, but its dysregulation can lead to several types of cancer. The SHH pathway is activated when the SHH protein binds to its receptor, Patched (PTCH). This interaction relieves the inhibition of another protein, Smoothened (SMO), leading to the activation of downstream signaling that promotes cell proliferation and survival. In many cancers, SHH and its downstream signaling components are often overexpressed. This overexpression can lead to increased cell proliferation, survival, and tumor growth.
634-	SIRT1	?	Sirtuin 1 protein			SIRT1 (Sirtuin 1) is a protein that plays a crucial role in various cellular processes, including metabolism, stress resistance, and longevity. In the context of cancer, SIRT1 has been found to have both tumor-suppressing and tumor-promoting functions, depending on the type of cancer and the cellular context. Expression Promotes: Breast, Prostate, Colorectal Cancer. Expression Suppresses: Leukemia, Liver Cancers.
1289-	SIRT2	↓	Sirtuin 2			SIRT2 is primarily localized in the cytoplasm but can also shuttle into the nucleus, where it regulates multiple cellular functions. It deacetylates various substrates including histones and non-histone proteins, thereby influencing gene expression, cell cycle progression, and cytoskeletal dynamics. SIRT2’s enzymatic activity is dependent on NAD⁺ levels, linking its function to the metabolic state of the cell. Lower expression levels often correlate with more aggressive disease and poorer prognosis in certain contexts, although some studies suggest that overexpression can also be deleterious in specific settings.
934-	SIRT3	↓	Sirtuin 3			SIRT3 (Sirtuin 3) is a protein that is a member of the sirtuin family of proteins, which are involved in various cellular processes, including metabolism, stress resistance, and longevity. In general, low SIRT3 expression is associated with: -Poor prognosis, Increased tumor size, Metastasis, Resistance to chemotherapy and radiation therapy, Poor response to treatment High SIRT3 expression is associated with: -Better prognosis, Smaller tumor size, Less metastasis, Better response to chemotherapy and radiation therapy, Better response to treatment SIRT3 also functions as a tumor suppressor by targeting the mitochondrial enzyme manganese superoxide dismutase (MnSOD), decreasing reactive oxygen species (ROS) production and maintaining genomic stability.
1135-	SIRT6	↓	Sirtuin 6			– SIRT6 is involved in maintaining genomic stability through its roles in DNA repair and chromatin remodeling. – By promoting efficient DNA repair, SIRT6 may help prevent the accumulation of genetic mutations that drive tumorigenesis. – In several studies, lower SIRT6 expression has been associated with more aggressive tumor behavior and poorer overall survival, supporting its role as a tumor suppressor in those contexts. – Conversely, in some cancers, higher SIRT6 expression has been linked to enhanced survival signaling or metabolic reprogramming that might support tumor growth, suggesting a possible oncogenic role.
1122-	SK	↑	Sphingosine kinases			Sphingosine kinases (commonly abbreviated as SK, with SK1 and SK2 being the main isoforms) are enzymes that catalyze the phosphorylation of sphingosine to produce sphingosine-1-phosphate (S1P). S1P is a bioactive signaling lipid that regulates cell growth, survival, migration, and angiogenesis. Elevated levels of S1P can promote proliferation and inhibit apoptosis (programmed cell death). -In many types of cancer, SK (especially SK1) is found to be overexpressed, leading to increased production of S1P. This can contribute to tumor growth, metastasis, and resistance to chemotherapy.
875-	SLC12A5	↑	SLC12A5			SLC12A5 is a gene that encodes a protein called KCC2, which is a potassium-chloride cotransporter. This protein plays a crucial role in maintaining the balance of potassium and chloride ions in cells, particularly in neurons. SLC12A5 has been found to be overexpressed in glioblastoma, breast, lung, CRC SLC12A5 has been found to promote cell proliferation in cancer cells.
1223-	SLC25A1	↑	CIC			SLC25A1 (also known as the mitochondrial citrate carrier, CIC) in cancer and its potential prognostic implications. SLC25A1 plays a central role in cellular metabolism by transporting citrate out of the mitochondria into the cytosol, where it can be used in lipid biosynthesis and energy production. • SLC25A1 facilitates the transport of citrate from the mitochondria to the cytosol. Once in the cytosol, citrate can be converted into acetyl-CoA, serving as a substrate for lipid synthesis and histone acetylation. • By linking mitochondrial metabolism with cytosolic biosynthetic pathways, SLC25A1 plays a key role in metabolic reprogramming—a hallmark of cancer. -In various cancers, including breast, lung, and colorectal cancers, elevated SLC25A1 expression has been associated—with varying degrees of consistency—with metabolic reprogramming that supports tumor growth and survival. As such, high SLC25A1 levels are often considered a marker of aggressive disease and may correlate with poorer prognosis.
579-	Sleep	?	Sleep Quality
413-	Slug	↑	transcription factor Slug			Slug is well known to promote tumor progression and metastasis through the epithelial-mesenchymal transition (EMT), causing loss of cell adhesion and polarity while conferring migratory and invasive properties. Slug/SNAI2: A transcription factor that belongs to the Snail family. It is best known for its role in regulating epithelial-to-mesenchymal transition (EMT). Expression: Upregulation of Slug in cancers is often associated with the induction of EMT. This causes cells to lose epithelial markers (like E-cadherin) and gain mesenchymal markers, leading to increased invasiveness. Metastatic Spread: By promoting EMT, high levels of Slug facilitate tumor cell dissemination and metastasis. Cancer Stem Cells: There is evidence suggesting that EMT, spurred by factors like Slug, can increase the proportion of cancer stem cells (CSCs). These CSCs are thought to be key players in tumor recurrence and maintenance. General Trend: High Slug expression in various cancers (including breast, colorectal, head and neck, and others) is frequently correlated with a more aggressive phenotype and poorer clinical outcomes.
1011-	Smad1	⇅				SMAD1 is a member of the SMAD family of proteins that are key intracellular mediators of the bone morphogenetic protein (BMP) signaling pathway. BMP/SMAD signaling plays a variety of roles in cell differentiation, proliferation, apoptosis, and migration. In some cancers, altered SMAD1 expression has been reported. For example, reduced expression can compromise the tumor-suppressive BMP signaling in some contexts, potentially allowing for unchecked cell proliferation. In other scenarios, particularly where BMP signaling promotes tumor progression or metastasis, elevated SMAD1 might be associated with a more aggressive phenotype. In cancers where SMAD1 functions predominantly as a tumor suppressor (via proper BMP signaling), lower levels of SMAD1 might be associated with a poorer prognosis. Conversely, in tumors where BMP signaling contributes to invasion or metastasis, higher SMAD1 expression may correlate with aggressive disease and worse outcomes.
283-	SMAD2	?	SMAD family member 2	CGL-Driver Genes	TSG	SMAD2 (SMAD family member 2) is a protein that plays a crucial role in the transforming growth factor-beta (TGF-β) signaling pathway, which is involved in various cellular processes, including cell growth, differentiation, and apoptosis. In some cancers, SMAD2 functions as a tumor suppressor. TGF-β signaling can inhibit cell proliferation and promote apoptosis in normal and early-stage cancer cells. In this context, SMAD2 helps to mediate these effects, and its loss or mutation can contribute to tumor progression. Conversely, in advanced cancers, TGF-β signaling can promote tumor progression and metastasis. In these cases, SMAD2 may contribute to the epithelial-to-mesenchymal transition (EMT), a process that allows cancer cells to acquire migratory and invasive properties. This dual role can make targeting the TGF-β/SMAD2 pathway challenging in cancer therapy.
556-	SMAD3	↑	SMAD3			Deletion or inhibition of Smad3 in the tumour microenvironment suppresses tumour growth, invasion and metastasis in two syngeneic mouse tumour models. Smad3 promotes cancer progression by inhibiting E4BP4-mediated NK cell development
284-	SMAD4	↓	SMAD family member 4	CGL-Driver Genes	TSG	SMAD4 is a critical tumor suppressor gene that plays a significant role in the TGF-β signaling pathway, which regulates various cellular processes, including cell growth, differentiation, and apoptosis. plays a critical role in the TGF-beta signaling pathway.
1012-	SMAD5	⇅				SMAD5 is a receptor-regulated SMAD (R-SMAD) protein that primarily transduces signals from the bone morphogenetic protein (BMP) family of cytokines. SMAD5, together with SMAD1 and SMAD8, is activated by BMP receptors. Once phosphorylated, it forms complexes with the common mediator SMAD4. In some studies, altered or reduced SMAD5 expression has been linked with the loss of BMP-mediated tumor-suppressive functions. This could, for example, compromise normal differentiation signals and enable unchecked proliferation. Conversely, in contexts where active BMP signaling may promote aspects of tumor progression (such as invasion or metastasis), altered activity or overexpression of SMAD5 may correlate with aggressive cancer phenotypes.
999-	Smad7	?				Smad7 is not a cell line but a protein—a member of the Smad family—that acts as an inhibitory regulator within the transforming growth factor-beta (TGF-β) signaling pathway. Smad7 is expressed widely across tissues and its expression is often upregulated in response to TGF-β stimulation, forming an auto-inhibitory loop. In some cancers, Smad7 is upregulated. This upregulation may help cancer cells bypass the growth-inhibitory effects of TGF-β signaling during early tumorigenesis, effectively blocking TGF-β's tumor suppressor role. • Conversely, in other cancer contexts, lower Smad7 levels might contribute to a more active TGF-β pathway, which in later stages can promote tumor invasion and metastasis. Thus, the role of Smad7 might shift depending on disease progression. • In many cases, the TGF-β signaling pathway acts as a double-edged sword in cancer: initially suppressing tumor growth but later facilitating processes like epithelial-to-mesenchymal transition (EMT), immune evasion, and metastasis. Smad7 is one of the key modulators in tipping this balance, so its expression levels will vary accordingly. In summary, while Smad7 is commonly upregulated in certain cancer cells to counteract TGF-β’s suppressor function during early tumorigenesis, its overall role and expression level can vary depending on the specific cancer type and stage.
285-	SMARCA4	↓	SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4	CGL-Driver Genes	TSG	SMARCA4, also known as BRG1, is a gene that encodes a protein involved in the SWI/SNF chromatin remodeling complex. This complex plays a crucial role in regulating gene expression by altering the structure of chromatin, making DNA more or less accessible for transcription. SMARCA4 is considered a tumor suppressor gene. Loss of function mutations in SMARCA4 can lead to the disruption of normal chromatin remodeling, contributing to uncontrolled cell growth and tumorigenesis. In many cancers, particularly those with mutations or deletions in the SMARCA4 gene, there is often a loss of expression of the SMARCA4 protein. This loss can lead to dysregulation of chromatin remodeling and contribute to tumorigenesis.
286-	SMARCB1	↓	SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily b, member 1	CGL-Driver Genes	TSG	SMARCB1, also known as INI1, is a gene that encodes a protein involved in the SWI/SNF chromatin remodeling complex, which plays a crucial role in regulating gene expression and maintaining genomic stability. In many cancers, particularly malignant rhabdoid tumors (MRTs), SMARCB1 is often found to be deleted or mutated, leading to a complete loss of protein expression. This loss is a hallmark of MRTs and is associated with their aggressive nature. SMARCB1 functions as a tumor suppressor. Its loss can lead to dysregulation of genes involved in cell cycle control, apoptosis, and differentiation, contributing to uncontrolled cell growth and tumor progression.
1202-	SMCT1	↓	SLC5A8			SLC5A8 (also known as SMCT1) is a sodium-coupled monocarboxylate transporter - Many studies suggest that SLC5A8 functions as a tumor suppressor. In normal tissues, SLC5A8 contributes to the cellular uptake of short-chain fatty acids (SCFAs) like butyrate. Butyrate is known to have histone deacetylase inhibitor activity, which can modulate gene expression in a way that suppresses tumor growth. -In cancer, loss or silencing of SLC5A8 is often observed. Epigenetic mechanisms such as DNA hypermethylation of the SLC5A8 promoter region are commonly cited as a reason for its downregulation. SLC5A8 is commonly downregulated in a variety of cancers. Its loss, often due to promoter hypermethylation, correlates with poorer outcomes in several tumor types, suggesting a tumor suppressor role. While sustained expression of SLC5A8 appears to be protective and is associated with a better prognosis in some cancers, the field is still evolving Inhibitors of DNA methylation induce reactivation of SLC5A8 procaine is a DNA-demethylating agent with growth-inhibitory effects in human cancer cells
748-	SMG1	↓	Suppressor of Morphogenetic Defects in Genitalia 1		gene	SMG1 (Suppressor of Morphogenetic Defects in Genitalia 1) is a gene that plays a crucial role in the regulation of DNA damage response and cell cycle progression. SMG1 is a phosphatidylinositol 3-kinase-related kinase (PIKK) that is activated in response to DNA damage. It phosphorylates and activates downstream targets, including p53, a tumor suppressor protein that plays a key role in preventing cancer. SMG1 also regulates the cell cycle by phosphorylating and inhibiting the activity of cyclin-dependent kinases (CDKs), which are essential for cell cycle progression. Studies have shown that SMG1 is frequently downregulated or mutated in various types of cancer, including breast, lung, and colon cancer.
287-	Smo	↑	G-protein-coupled receptor-like 7-pass transmembrane protein Smoothened	CGL-Driver Genes	HH Oncogene	smoothened homolog (Drosophila) SMO, or Smoothened, is a protein that plays a crucial role in the Hedgehog signaling pathway, which is important for cell growth, differentiation, and tissue patterning during embryonic development. Inhibitors of SMO, such as vismodegib and sonidegib, have been developed as targeted therapies for cancers associated with aberrant Hedgehog signaling. SMO (Smoothened): - A G protein-coupled receptor (GPCR)-like protein that is a critical component of the Hedgehog (Hh) signaling pathway. - Functions in transmitting the Hedgehog signal from the cell surface to intracellular effectors, culminating in changes in gene expression. Aberrant Activation of the Hedgehog Pathway: - In many cancers, mutations or dysregulations in pathway components lead to ligand-independent or ligand-dependent activation of SMO. - This inappropriate activation can result in enhanced cell proliferation, survival, and stem cell-like Several cancers exhibit overexpression of SMO or activating mutations leading to Hedgehog pathway activation. Smoothened (SMO) is a critical mediator of the Hedgehog signaling pathway, with aberrant activation contributing to tumor growth, progression, and resistance to therapy. High expression or activating mutations in SMO are linked with a poor prognosis in certain cancer types, particularly in cancers that are dependent on Hedgehog pathway signaling such as basal cell carcinoma and medulloblastoma. By targeting SMO with specific inhibitors, researchers and clinicians are addressing one of the key drivers of tumorigenesis in these settings.
376-	Snail	↑	Snail			Snail gene may show a role in recurrence of breast cancer by downregulating E-cadherin and inducing an epithelial to mesenchymal transition. Snail promotes metastasis of breast cancer cells and overexpression of Snail is a biomarker of poor clinical outcome for patients with breast cancer. Snail, a repressor of E-cadherin and an inducer of EMT Snail (SNAI1): A transcription factor that plays a key role in the regulation of the epithelial-to-mesenchymal transition (EMT). It suppresses the expression of epithelial markers (such as E-cadherin) and upregulates mesenchymal markers, facilitating changes in cell adhesion and motility. EMT Induction: Snail actively represses genes such as E-cadherin, a protein critical for cell–cell adhesion. Its upregulation leads to a loss of epithelial characteristics and the acquisition of a mesenchymal phenotype, enhancing migratory potential. Invasion and Metastasis: Through EMT induction, Snail facilitates tumor cell dissemination and invasion into surrounding tissues, thereby playing a central role in metastasis. Elevated levels of Snail have been observed in a variety of cancers, including breast, colorectal, pancreatic, and head and neck cancers. Elevated Snail expression is frequently associated with a worse prognosis, including lower overall survival rates and increased likelihood of metastasis.
659-	SNCG	↑	SNCG gene			SNCG gene, also known as the synuclein gamma gene, is a gene that encodes a protein called synuclein gamma. This protein is a member of the synuclein family, which also includes alpha-synuclein and beta-synuclein. The SNCG gene is located on chromosome 10q23 and is expressed in various tissues, including the brain, breast, and other organs. The synuclein gamma protein is involved in several cellular processes, including cell signaling, cell growth, and cell survival. Dysregulation of the SNCG gene has been implicated in several types of cancer, including breast cancer, ovarian cancer, and neurodegenerative diseases such as Parkinson's disease and Alzheimer's disease. In cancer, overexpression of the SNCG gene has been associated with tumor progression, metastasis, and poor prognosis.
663-	SOCS-3	↓	Suppressor of Cytokine Signaling 3			SOCS-3) is a protein that plays a crucial role in regulating the immune response and inflammation. It is a negative regulator of the JAK/STAT signaling pathway, which is involved in the signaling of various cytokines and growth factors. Research has shown that SOCS-3 is often downregulated or inactivated in various types of cancer, including breast, lung, colon, and liver cancer. This downregulation can lead to an overactivation of the JAK/STAT pathway, resulting in the promotion of cell proliferation, survival, and angiogenesis (the formation of new blood vessels).
288-	SOCS1	↓	suppressor of cytokine signaling 1	CGL-Driver Genes	TSG	SOCS1 (Suppressor of Cytokine Signaling 1) is a protein that plays a critical role in regulating the immune response and cellular signaling pathways. It is part of the SOCS family of proteins, which are known to inhibit cytokine signaling and modulate various cellular processes, including cell growth, differentiation, and apoptosis. SOCS1 is often considered a tumor suppressor because it can inhibit pathways that promote cell proliferation and survival, such as the JAK/STAT signaling pathway. Dysregulation of this pathway is commonly observed in various cancers. In many cancers, SOCS1 expression is found to be downregulated or silenced. This can occur through mechanisms such as promoter methylation, histone modifications, or genetic mutations. The loss of SOCS1 expression can lead to unchecked activation of signaling pathways, particularly the JAK/STAT pathway, which is associated with increased cell proliferation and survival.
298-	SOD	↑	superoxide dismutase			SOD, or superoxide dismutase, is an important antioxidant enzyme that plays a crucial role in protecting cells from oxidative stress. It catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide. SOD Isoforms: There are three main isoforms of SOD: SOD1 (cytosolic): Often found to be overexpressed in certain tumors, which may help cancer cells survive in oxidative environments. SOD2 (mitochondrial): Plays a critical role in protecting mitochondria from oxidative damage. Its expression can be upregulated in some cancers, contributing to tumor growth and resistance to therapy. SOD3 (extracellular): Its role in cancer is less well understood, but it may have implications in the tumor microenvironment and metastasis. The expression levels of SOD can serve as a prognostic indicator in some cancers. For example, high levels of SOD expression have been associated with poor prognosis in certain types of tumors, potentially due to their role in promoting tumor cell survival and resistance to therapies.
1052-	SOD1	⇅	superoxide dismutase 1			SOD1 (superoxide dismutase 1) is a key antioxidant enzyme that catalyzes the dismutation of superoxide radicals into oxygen and hydrogen peroxide. In several cancers including breast, lung, HCC, and others, alterations in SOD1 expression have been observed, reflecting its role in managing oxidative stress. • Elevated SOD1 levels are sometimes associated with aggressive tumor behavior, therapy resistance, or decreased apoptosis due to enhanced ROS detoxification. • Conversely, the protective role of antioxidants can also mitigate oxidative mutation loads, leading to context-dependent and occasionally favorable outcomes. In non-small cell lung cancer (NSCLC), increased SOD1 levels have been reported in some cohorts, potentially as a mechanism to cope with high reactive oxygen species (ROS) levels.
935-	SOD2	⇅	MnSOD		protein	manganese superoxide dismutase (MnSOD, also known as SOD2) SOD2 (Superoxide Dismutase 2) is a protein that is a member of the superoxide dismutase family of enzymes, which are involved in the detoxification of superoxide radicals. -MnSOD is localized in the mitochondria and plays a key role in detoxifying superoxide radicals, thereby limiting oxidative damage and maintaining mitochondrial integrity. • By modulating ROS levels, MnSOD influences cellular signaling pathways involved in proliferation, apoptosis, and metabolic adaptation—all of which are critical during tumorigenesis. Typically low SOD2 expression in cancers, with poor prognosis -Increased MnSOD levels may help tumor cells manage the high levels of ROS resulting from rapid cell division and metabolic alterations, which can contribute to tumor progression. - Some prognostic studies associate high levels of MnSOD with resistance to apoptosis and poorer patient outcomes; however, findings are not entirely consistent across all studies. • Depending on the tumor type and the balance with other antioxidant systems, high MnSOD can be associated with either favorable or unfavorable clinical outcomes, reflecting its dual roles in cancer biology.
1318-	sonoP	↓	sonoporation			Sonoporation is a technique that uses ultrasound waves to transiently increase the permeability of cell membranes, allowing for the enhanced delivery of drugs, genes, or other therapeutic agents into cells. -Microbubbles (gas-filled contrast agents commonly used in ultrasound imaging) are often administered alongside the therapeutic agent. When exposed to ultrasound, these microbubbles oscillate and can collapse (a process known as cavitation). This cavitation enhances the permeability of nearby cell membranes, thus facilitating drug or gene uptake.
1150-	sonoS	∅	sonosensitizer			sonosensitizer is a product that works with SDT (sonic dynamic therapy)
656-	SOX2	↑	SOX2			SOX2 is a transcription factor that plays a crucial role in the development and maintenance of various cell types, including stem cells and progenitor cells. In the context of cancer, SOX2 has been found to be overexpressed in several types of tumors, including lung, breast, and esophageal cancers. Overexpressed in: Lung, Breast, Esophageal, Prostate, GBM, CRC.
1060-	SOX4	↑	SRY‐box transcription factor 4			SOX4 belongs to the SOX (SRY-related HMG-box) family of transcription factors and plays a critical role in embryonic development, differentiation, and cell survival. • In cancer, SOX4 has been implicated in processes such as epithelial-to-mesenchymal transition (EMT), invasion, metastasis, and resistance to apoptosis. In many cancers—including breast, colorectal, lung, ovarian, and pancreatic cancers—high SOX4 expression is generally associated with a more aggressive tumor phenotype and poorer clinical outcomes.
289-	SOX9	↑	SRY (sex determining region Y)-box 9	CGL-Driver Genes	TSG	SOX9 (SRY-box transcription factor 9) is a transcription factor that plays a crucial role in various biological processes, including embryonic development, cell differentiation, and tissue homeostasis. SOX9 has been implicated in the development and progression of several types of cancer, including breast, prostate, colorectal, and pancreatic cancers. It can promote tumor growth by regulating genes involved in cell proliferation, survival, and metastasis.
506-	Sp1/3/4	?	Specificity Protein			SP2 (Specificity Protein 2) and SP3 (Specificity Protein 3) are also members of the Sp/KLF (Sp1/Krüppel-like factor) family of transcription factors, similar to SP1. They share some functional similarities but also have distinct roles in cellular processes and cancer biology. SP1 is often overexpressed in various types of cancer, including breast, prostate, and lung cancers.
517-	SPARC	⇅	secreted protein acidic and rich in cysteine			SPARC (a secreted protein acidic and rich in cysteine) has a reputation for being potent anti-cancer and anti-obesity molecule. It is one of the first known matricellular protein that modulates interactions between cells and extracellular matrix (ECM) and is associated with the ‘balance’ of white adipose tissue (WAT) as well as lipogenesis and lipolysis during adipogenesis. Adipogenesis is an indication for the development of obesity and has been related to a wide variety of cancers including breast cancer, endometrial cancer, esophageal cancer, etc. In highly metastatic tumors, such as glioblastomas, melanoma, breast cancer and prostate cancer, SPARC promotes bone metastasis and epithelial-mesenchymal transition (EMT). In contrast, this protein acts as an anti-tumor factor in anti-angiogenesis, pro-apoptosis, cell proliferation inhibition and cell cycle arrest in less metastatic tumors, such as neuroblastoma, ovarian cancer, pancreatic cancer, colorectal cancer and gastric cancer. SPARC is an essential Ca -binding protein involved in cell proliferation, di�erentiation, and migration.
290-	SPOP	?	speckle-type POZ protein	CGL-Driver Genes	Oncogene	SPOP (Speckle-type POZ protein) is a gene that encodes a protein involved in various cellular processes, including transcriptional regulation and protein degradation. SPOP mutations are most commonly associated with prostate cancer. In this context, SPOP is often found to be mutated rather than simply overexpressed or underexpressed. These mutations can lead to the loss of its normal function, which is to promote the degradation of certain proteins, including the androgen receptor. This dysregulation can contribute to the development and progression of prostate cancer.
406-	SPP1	?	Secreted phosphoprotein 1			SPP1 plays a crucial role in cancer progression, metastasis, and treatment resistance. High levels of SPP1 expression have been detected in various cancer types
291-	Src	↑	Src kinase		Oncogene	Src family of tyrosine kinases, which are a group of proteins involved in the regulation of various cellular processes, including cell growth, differentiation, and survival. Src is overexpressed in several types of cancer, including breast, colon, lung, and prostate cancers.
732-	SRD5A1	↑	SRD5A1		gene	SRD5A1 is a gene that encodes the enzyme 5-alpha-reductase type 1. This enzyme plays a crucial role in the conversion of testosterone to dihydrotestosterone (DHT), a potent androgen hormone. Elevated Expression in: prostate, breast, ovarian, endometrial, adrenal, testcular, uterine, adenocarcinoma.
959-	SREBF2	↑	Sterol Regulatory Element Binding Factor 2			The SREBF2 gene (Sterol Regulatory Element Binding Factor 2) is a key regulator of lipid metabolism, particularly in the synthesis of cholesterol and fatty acids. The SREBF2 gene is overexpressed in various types of cancer. SREBF2 gene is a key regulator of lipid metabolism and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.
1034-	SREBP1	↑	sterol regulatory element-binding protein 1			SREBP1 is a key transcription factor that regulates genes involved in fatty acid and triglyceride synthesis. It primarily governs lipid metabolism by controlling the expression of enzymes required for de novo lipogenesis, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC), among others. two main isoforms—SREBP1a and SREBP1c—with SREBP1c being more involved in the regulation of lipogenesis in metabolic tissues. Many cancers display elevated levels of SREBP1 activity. Increased expression or activation of SREBP1 supports the metabolic reprogramming that is characteristic of cancer cells, enabling them to meet the enhanced lipid requirements for membrane synthesis and energy storage during rapid cell proliferation. Elevated SREBP1 activity is often linked to more aggressive cancer phenotypes. High SREBP1 levels can drive rapid proliferation, metastasis, and resistance to certain therapies, thereby correlating with poorer clinical outcomes in several cancers.
1132-	SREBP2	↑	Sterol Regulatory Element-Binding Protein 2			Sterol Regulatory Element-Binding Protein 2 (SREBP-2) SREBP-2 is a key transcription factor that primarily regulates cholesterol biosynthesis and uptake. In recent years, its dysregulation has been linked to altered lipid metabolism within tumors, potentially affecting tumor growth, metastasis, and response to treatment. -(SREBP-2) is a pivotal transcriptional factor in cholesterol metabolism. – SREBP-2 controls the transcription of genes involved in cholesterol biosynthesis and uptake (e.g., HMG-CoA reductase, LDL receptor). – Cancer cells may upregulate SREBP-2 as part of metabolic rewiring to meet the demands of rapid proliferation. – Elevated SREBP-2 expression has been observed in several tumor types, including prostate, breast, and hepatocellular carcinoma. – High expression levels are sometimes associated with aggressive tumor phenotypes, increased proliferative capacity, and a higher incidence of metastasis. • SREBP-2 plays a critical role in maintaining lipid homeostasis, and its dysregulation in cancer can contribute to tumor growth and aggressiveness. • Elevated SREBP-2 expression is generally associated with enhanced tumor cell proliferation, increased risk of metastasis, and in some instances, a poorer prognosis.
292-	SRSF2	?	SRSF2 serine/arginine-rich splicing factor 2	CGL-Driver Genes	Oncogene	SRSF2 (Serine/Arginine-Rich Splicing Factor 2) is a gene that encodes a protein involved in the regulation of pre-mRNA splicing. It plays a crucial role in the processing of RNA and the production of mature mRNA, which is essential for proper gene expression. SRSF2 is a splicing factor, and its altered expression can lead to changes in the splicing of various pre-mRNAs. This can result in the production of oncogenic isoforms of proteins or the loss of tumor suppressor isoforms, contributing to cancer development and progression.
665-	SSAT	?	Spermidine/Spermine N1-Acetyltransferase		gene	SSAT gene (Spermidine/Spermine N1-Acetyltransferase) is a gene that encodes an enzyme involved in the regulation of polyamine metabolism. Polyamines, such as spermidine and spermine, are small molecules that play a crucial role in various cellular processes, including cell growth, proliferation, and differentiation. The SSAT enzyme is responsible for the acetylation of spermidine and spermine, which is a key step in the degradation of these polyamines. The SSAT gene is located on chromosome 2q31.1 and is expressed in various tissues, including the liver, kidney, and brain. Dysregulation of the SSAT gene has been implicated in various diseases, including cancer. Overexpression of the SSAT gene has been observed in certain types of cancer, such as breast, prostate, and colon cancer. Overexpression: Breast, Prostate, Colon Underexpressed: Ovarian, lung
1047-	SSBP1	⇅	single-stranded DNA binding protein 1			While many studies suggest that altered SSBP1 expression is linked to tumor aggressiveness and patient outcomes, the direction of change (upregulation or downregulation) and the prognostic implications can vary between cancer types. For instance: • In breast and colorectal cancers, lower SSBP1 expression has been associated with enhanced invasiveness and poorer prognosis. • In lung cancer, higher SSBP1 expression in some studies correlates with more aggressive disease features and unfavorable outcomes.
780-	STAC2	↑	SH3 and cysteine-rich domain 2		protein	STAC2 (SH3 and cysteine-rich domain 2) is a a novel voltage-gated calcium channel protein. Overexpressed in: breast, prostate, lung, ost, CRC cancers STAC2 also interacts with other signaling pathways to promote cancer progression. For example, STAC2 interacts with the PI3K/AKT signaling pathway to promote cell survival and the NF-κB signaling pathway to promote inflammation and cell proliferation. target genes of STAC2 include: VEGF, MMPs, BCL-2, Cyclin D1
293-	STAG2	↓	stromal antigen 2	CGL-Driver Genes	TSG	STAG2 (Stag2, or Stromal Antigen 2) is a gene that encodes a protein involved in the cohesion of sister chromatids during cell division. It is part of the cohesin complex, which plays a crucial role in maintaining genomic stability. In many cancers, STAG2 expression is often downregulated due to mutations, deletions, or epigenetic changes.
731-	StAR	↑	Steroidogenic Acute Regulatory protein		protein	StAR (Steroidogenic Acute Regulatory protein) is a protein that plays a crucial role in the regulation of steroid hormone biosynthesis. It is involved in the transfer of cholesterol into the mitochondria, where it is converted into pregnenolone, the precursor to all steroid hormones. StAR is overexpressed in various types of cancer, including breast, prostate, and ovarian cancer. This overexpression is often associated with increased steroid hormone production, which can promote tumor growth and progression.
294-	STAT	↑	Signal transducer and activator of transcription	CGL-CS		STAT proteins, or Signal Transducer and Activator of Transcription proteins, are a family of transcription factors that play a crucial role in various cellular processes, including cell growth, differentiation, and apoptosis. They are activated by cytokines and growth factors and are involved in signaling pathways that can influence cancer development and progression. STAT proteins can promote cell division and survival, leading to increased tumor growth. Many cancers exhibit overexpression of certain STAT proteins, particularly STAT3 and STAT5.
370-	STAT1	↓	Signal transducer and activator of transcription 1			STAT1 (Signal Transducer and Activator of Transcription 1) is a transcription factor that plays a crucial role in various cellular processes, including immune response, cell growth, and apoptosis. Unregulated in some cancers. High STAT1 expression has been associated with improved prognosis and reduced metastasis. Low STAT1 expression has been linked to poor prognosis and reduced survival.
738-	STAT2	↓	Signal Transducer and Activator of Transcription 2		protein	STAT2 (Signal Transducer and Activator of Transcription 2) is a protein that plays a crucial role in the regulation of immune responses, particularly in the context of viral infections and cancer. STAT2 has been shown to have both tumor-suppressive and tumor-promoting functions, depending on the type of cancer and the cellular context. High STAT2 expression has been associated with better prognosis and improved response to therapy. Low STAT2 expression has been linked to poor prognosis and reduced survival. Expression varies depending on Cancer
373-	STAT3	↑	Signal transducer and activator of transcription 3		Oncogene	Stat3 (Signal Transducer and Activator of Transcription 3) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, survival, differentiation, and immune response. Stat3 is frequently found to be constitutively activated in many types of cancers, including breast, prostate, lung, and head and neck cancers. (associated with poor prognosis and reduced survival.) -STAT3 is typically activated by cytokines (such as IL-6) and growth factors binding to their respective receptors. -Activated STAT3 upregulates the expression of genes that promote cell cycle progression (e.g., cyclin D1) and anti-apoptotic proteins (e.g., Bcl-2, Bcl-xL).
371-	STAT4	↓	Signal transducer and activator of transcription 4			STAT4 (Signal Transducer and Activator of Transcription 4) is a transcription factor that plays a significant role in the immune response and has been implicated in various biological processes, including inflammation and cell proliferation. High STAT4 expression has been associated with improved prognosis and reduced metastasis.
372-	STAT5	↑	Signal transducer and activator of transcription 5			Signal Transducer and Activator of Transcription 5 (STAT5) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, differentiation, and survival. STAT5 can function as an oncogene in certain types of cancer. Its persistent activation has been associated with the development and progression of various malignancies, including breast cancer, prostate cancer, and hematological cancers like leukemia and lymphoma. High STAT5 expression has been associated with poor prognosis and increased metastasis.
1157-	STAT6	↑	Signal Transducer and Activator of Transcription 6			Signal Transducer and Activator of Transcription 6 (STAT6) is a transcription factor well-known for its role in mediating the effects of cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). Its activation and subsequent nuclear translocation trigger transcription of target genes that regulate immune responses, cell proliferation, and differentiation. -STAT6 expression and activation have been documented in various malignancies such as lymphomas, breast cancer, and certain gastrointestinal cancers. -Elevated or constitutive activation of STAT6 in tumors has been associated with a poorer prognosis in some cancer types, potentially due to its roles in promoting survival, proliferation, and immune evasion. It also affects the composition and function of immune infiltrates within the tumor. Through modulating cytokine expression profiles, activated STAT6 can lead to a microenvironment that favors Th2 responses and suppresses effective anti-tumor immunity. This dual role—impacting both intrinsic tumor cell biology and the extrinsic immune context—complicates the interpretation of STAT6 as a prognostic marker.
963-	STEAP3	↑	Six Transmembrane Epithelial Antigen of the Prostate 3			The STEAP3 gene (Six Transmembrane Epithelial Antigen of the Prostate 3) is a metalloreductase that plays a crucial role in the regulation of iron and copper metabolism. The STEAP3 gene is overexpressed in various types of cancer. STEAP3 gene is a key regulator of iron and copper metabolism and is overexpressed in various types of cancer. Its expression is associated with poor prognosis and increased risk of metastasis and recurrence.
296-	STK11	↓	serine/threonine kinase 11	CGL-Driver Genes	TSG	also known as serine/threonine kinase 11 STK11, also known as LKB1 (Liver Kinase B1), is a tumor suppressor gene that plays a crucial role in regulating cell metabolism, growth, and polarity. enzymatic activity is crucial for regulating various cellular processes, including metabolism, cell growth, and cell cycle progression. The gene's role as a tumor suppressor is linked to its ability to control these processes, and mutations in STK11 can lead to the development of various cancers. In many cancers, particularly those associated with mutations in the STK11 gene, there is often a loss of STK11 expression or function.
578-	Strength	?	physical strength
375-	Sufu	↓	Sufu gene		Gene	a mutation in the SUFU gene, this means you have a condition called Gorlin syndrome or nevoid basal cell carcinoma syndrome (NBCCS). The expression levels of SUFU were significantly decreased in gastric cancer cells and the tumor tissues of gastric cancer patients. Sufu is a key negative regulator of the Hedgehog (Hh) signaling pathway, which is involved in cell differentiation, proliferation, and tissue patterning. • By inhibiting Gli transcription factors downstream of Hh signaling, Sufu helps moderate pathway activity. • Aberrant Hh pathway activation—often through genetic or epigenetic disruption of Sufu—has been implicated in the development and progression of various cancers. Sufu serves as a negative regulator of the Hh pathway, and its reduced expression or loss-of-function mutations can result in increased Hh signaling, promoting tumorigenesis.
299-	survivin	↑			antiapoptosis protein	Survivin is a potent anti-apoptosis protein that is differentially expressed in cancer and therefore constitutes an important anti-cancer target [49]. Moreover, high expression of survivin plays important role in resistance to chemo- and radiotherapy and has been shown to be related to unfavorable outcome for medulloblastomas "Survivin" is a protein that plays a crucial role in regulating cell division and inhibiting apoptosis (programmed cell death). It is part of the inhibitor of apoptosis (IAP) family and is often overexpressed in various types of cancer.
838-	SUZ12	↑	Suppressor of zeste 12			SUZ12 (Suppressor of zeste 12) is a protein that plays a crucial role in the regulation of gene expression through histone modification. It is a key component of the Polycomb repressive complex 2 (PRC2), which is involved in the silencing of genes through histone methylation. Overexpression of SUZ12 has been observed in many types of cancer, and it is often associated with poor prognosis and reduced survival rates.
814-	SVCT-2	↑	Sodium-dependent Vitamin C Transporter 2			SVCT-2 is a protein that plays a role in the transport of vitamin C (ascorbic acid) into cells. SVCT-2 is expressed in: 70% breast, 60% lung, 80% CRC, 50% Prostate, 70% ovarian, 60% Pancreatic, 50% liver, 60% stomach, 50% esophageal, 60% Head and Neck, 50% Melanoma, 70% GBM, 60% Medulloblastoma. SVCT-2 was involved in the transport of vitamin C into lung cancer cells and that its inhibition reduced cancer cell growth and survival.
1283-	SXR	↑	PXR-Steroid and Xenobiotic Receptor			SXR (Steroid and Xenobiotic Receptor, also known as Pregnane X Receptor, PXR) -SXR/PXR is a nuclear receptor that is primarily known for its role in detecting and mediating the metabolism and clearance of xenobiotics, drugs, and endogenous compounds. - Since SXR/PXR regulates drug-metabolizing enzymes and transporters, overexpression in tumor cells may lead to increased metabolism and clearance of anticancer drugs, potentially contributing to chemoresistance. – Some studies suggest that high SXR/PXR expression might be linked to more aggressive tumor behavior in certain cancers, such as breast, prostate, and gastrointestinal cancers, as it can alter cellular metabolic states and modulate survival pathways.
811-	Symptoms	?	Symptoms		marker	Cancer Symptoms
896-	T-cadherin	↑	T-cadherin/CDH13			T-cadherin, also known as cadherin 13 (CDH13), is a member of the cadherin family of cell adhesion molecules. T-cadherin is often overexpressed in certain types of cancer, including breast, prostate, and ovarian cancer. This overexpression has been associated with tumor progression, metastasis, and poor patient outcomes.
300-	T-Cell	↓	T lymphocytes		white blood cell	T cells are white blood cells that play a central role in the adaptive immune response. Subsets and Function: Cytotoxic T Cells (CD8+): Recognize and kill infected or malignant cells. Helper T Cells (CD4+): Assist in orchestrating the immune response by secreting cytokines and supporting the functions of other immune cells. T cells, particularly CD8+ cytotoxic T cells, can recognize tumor antigens presented on major histocompatibility complex (MHC) molecules and directly kill malignant cells. Regulatory T Cells (Tregs): Maintain immune tolerance and prevent autoimmunity but may also suppress anti-tumor responses in the tumor microenvironment. Tumor-Infiltrating Lymphocytes (TILs): Tumor Microenvironment: The presence of T cells within tumors, often referred to as tumor-infiltrating lymphocytes, is a key indicator of an ongoing anti-tumor immune response. Regulatory T Cells (Tregs): Tregs within the tumor environment may inhibit the activity of cytotoxic T cells through the secretion of immunosuppressive cytokines (e.g., IL-10, TGF-β), thus allowing tumors to evade the immune response. In many cancers, a robust T cell infiltrate is correlated with a better overall survival, lower rates of relapse, and improved responses to therapy. Assessing the type, density, and activation state of T cells in the tumor microenvironment can provide valuable prognostic information. High levels of active, cytotoxic T cells generally indicate a better prognosis.
1046-	T-SOD	⇅	tissue superoxide dismutases			tissue superoxide dismutases (T‐SOD)—referring generally to the family of SOD enzymes (e.g., SOD1, SOD2, and SOD3) responsible for detoxifying reactive oxygen species (ROS)—in the context of cancer. Superoxide dismutases (SODs) are antioxidant enzymes that catalyze the conversion of the superoxide anion (O₂•–) into hydrogen peroxide and oxygen. Oxidative stress plays a dual role in cancer: while moderate levels of ROS can promote cell proliferation and survival signaling, excessive ROS can cause cellular damage and trigger apoptosis. Alterations in SOD expression may therefore contribute to either tumor suppression or promotion depending on the context: • Upregulation of SOD can protect normal and cancer cells against oxidative damage, sometimes supporting tumor cell survival under stress. • Conversely, low SOD activity may lead to increased ROS, DNA damage, and mutagenesis, thereby contributing to tumor initiation.   – The specific impact of changes in T‐SOD levels often depends on the isoform in question, the type of cancer, and the balance with other oxidative stress regulators.
626-	TAC	↓	total antioxidant capacity			Total antioxidant capacity (TAC) refers to the ability of a biological sample (such as blood, tissues, or food) to counteract oxidative stress by neutralizing free radicals and reactive oxygen species (ROS). May have reduced levels in cancers.
1288-	talin	↑	talin			Talin is a cytoskeletal protein that plays a central role in linking integrins to the actin cytoskeleton. Two major isoforms exist—talin-1 and talin-2 -Talin serves as a key mediator of integrin activation and cytoskeletal organization, functions that underpin its role in regulating cell adhesion, migration, and invasion. -In several cancers—including breast, prostate, and colorectal cancers—elevated expression of talin (most notably talin-1) has been associated with more aggressive tumor behavior, increased metastatic potential, and poorer clinical outcomes.
912-	TAMS	↑	tumor-associated macrophages			Tumor-Associated Macrophages (TAMs) TAMs are a type of immune cell found abundantly within the tumor microenvironment. They originate from circulating monocytes that differentiate into macrophages upon migrating into tissues. TAMs produce various growth factors, such as epidermal growth factor (EGF) and transforming growth factor-beta (TGF-β), which can directly stimulate tumor cell proliferation and survival. By secreting vascular endothelial growth factor (VEGF) and other pro-angiogenic factors, TAMs facilitate the formation of new blood vessels, ensuring that tumors receive an adequate supply of oxygen and nutrients. High densities of TAMs are found in many tumor types, including breast, lung, colorectal, and pancreatic cancers, among others. high infiltration of TAMs in tumors is correlated with worse overall survival, aggressive disease, increased metastatic potential, and resistance to therapy.
911-	TANs	↑	tumor-associated neutrophils
432-	TAp63α	↓	TAp63α			TAp63α is a protein isoform of the p63 gene, which is a member of the p53 family of transcription factors. p63 is involved in various cellular processes, including development, cell cycle regulation, and apoptosis. TAp63α has been implicated in cancer development and progression. It is often overexpressed in various types of cancer, including breast, lung, and head and neck cancers. The overexpression of TAp63α has been associated with poor prognosis and aggressive tumor behavior. In multiple cancers, lower expression of the tumor‐suppressive TAp63α isoform tends to correlate with a more aggressive clinical course and poorer overall survival
301-	TarDef DNArep	?	Target deficient DNA repair	HalifaxProj		In cancer cells, DNA repair mechanisms can be altered or deficient, which can contribute to genomic instability and tumor progression
857-	TAS	↑	Tumor Angiogenesis Score		measure	TAS (Tumor Angiogenesis Score) is a measure used to assess the growth of new blood vessels in tumors, which is a key factor in cancer progression. The TAS score is typically calculated by analyzing the density of microvessels in a tumor sample. Microvessels are small blood vessels that are less than 10 micrometers in diameter. The score is usually expressed as a number of microvessels per unit area of tumor tissue. A high TAS score is often associated with a more aggressive cancer and a poorer prognosis.
858-	TASc	↑	Tumor Angiogenesis Score		measure	TAS (Tumor Angiogenesis Score) is a measure used to assess the growth of new blood vessels in tumors, which is a key factor in cancer progression. The TAS score is typically calculated by analyzing the density of microvessels in a tumor sample. Microvessels are small blood vessels that are less than 10 micrometers in diameter. The score is usually expressed as a number of microvessels per unit area of tumor tissue. A high TAS score is often associated with a more aggressive cancer and a poorer prognosis.
1231-	tau	?	tau			In healthy neurons, tau binds to and stabilizes microtubules, which are essential for maintaining cell structure and facilitating axonal transport. In AD, tau becomes abnormally hyperphosphorylated. This excessive phosphorylation reduces its affinity for microtubules, leading to destabilization of the cytoskeletal structure.
678-	TAZ	↑	Transcriptional Coactivator with PDZ-binding motif			transcriptional coactivators that play crucial roles in the Hippo signaling pathway, which regulates cell growth, proliferation, and survival. TAZ and YAP are both phosphorylated and inhibited by the Hippo pathway, which leads to their cytoplasmic retention.
862-	TBARS	↑	Thiobarbituric Acid Reactive Substances		measure	TBARS (Thiobarbituric Acid Reactive Substances) is a measure of lipid peroxidation, which is the oxidative degradation of lipids. Lipid peroxidation is a process in which free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs), leading to cell damage. Research has shown that TBARS levels are often elevated in cancer patients. This is because cancer cells have higher levels of reactive oxygen species (ROS) than normal cells, which can lead to increased lipid peroxidation.
1303-	TBX15	?	T-box transcription factor 15			TBX15 (T-box transcription factor 15) is a member of the T-box family of transcription factors, which are primarily known for their roles in embryonic development and tissue differentiation. • TBX15 expression levels can vary depending on the tissue type and the nature of the tumor. In some studies, aberrant (either increased or decreased) TBX15 expression has been observed in certain cancers compared to corresponding normal tissues.
818-	TCA	⇅	Tricarboxylic Acid Cycle		enzymes	Tricarboxylic Acid (TCA) cycle, also known as the Citric Acid cycle or Krebs cycle, is a key metabolic pathway that plays a central role in cellular energy production. The TCA cycle is a series of chemical reactions that occur in the mitochondria and involve the breakdown of acetyl-CoA, a molecule produced from the breakdown of carbohydrates, fats, and proteins. The TCA cycle produces: 1.NADH and FADH2 2.ATP 3.GTP expression of TCA cycle enzymes is often downregulated in cancer cells Since cancer cells often exhibit rewired metabolism, including alterations in the use of the TCA cycle, researchers are exploring potential therapeutic interventions that target metabolic enzymes or pathways. TCA cycle is essential for normal cellular metabolism, its role in cancer is multifaceted. Cancer cells often reprogram their metabolism—including the TCA cycle—to support rapid growth, adapt to hypoxia, and manage oxidative stress. Mutations in key TCA cycle enzymes generate oncometabolites that further contribute to cancer progression by disrupting normal cellular regulation. Rather than saying the TCA cycle is globally over- or underexpressed in cancer, it is more accurate to say that cancer cells reprogram the cycle—with selective upregulation of parts important for biosynthesis and survival and mutations or downregulation of other parts—to best support their growth and survival in a challenging microenvironment. Oncometabolites -Some metabolites in the Krebs cycle, when accumulated to abnormal levels due to genetic mutations or enzyme deficiencies, are termed “oncometabolites” because they can promote tumorigenesis. -Mutations in succinate dehydrogenase (SDH) can lead to accumulation of succinate. - mutations in fumarate hydratase (FH) result in an accumulation of fumarate -Mutations in isocitrate dehydrogenase (IDH1 and IDH2) result in a neomorphic enzyme activity that converts α-ketoglutarate (α-KG) to 2-hydroxyglutarate:
414-	TCF	↑	T-cell factor (Tcf) family			T-cell factor (Tcf) is a family of transcription factors that play a crucial role in the Wnt signaling pathway, which is important for cell proliferation, differentiation, and survival. Tcf proteins, particularly Tcf1, Tcf3, Tcf4, and Tcf7L2, interact with β-catenin, a key mediator of Wnt signaling, to regulate the expression of target genes involved in various cellular processes. Tcf factors are involved in maintaining the properties of cancer stem cells (CSCs), which are thought to drive tumor initiation, metastasis, and resistance to therapy. The Wnt/Tcf signaling pathway is often activated in CSCs, promoting their self-renewal and survival. Tcf4: Often overexpressed due to mutations in the APC gene, leading to increased Wnt signaling and tumorigenesis
967-	TCF-4	⇅	Transcription Factor 4			TCF4 gene (Transcription Factor 4) is a transcription factor that plays a crucial role in the Wnt/β-catenin signaling pathway, which is involved in cell proliferation, differentiation, and survival. TCF4 gene has been found to be: Amplified in 15% of breast cancer cases Mutated in 10% of lung cancer cases Deleted in 20% of prostate cancer cases Methylated in 30% of colorectal cancer cases
302-	Telomerase	↑	Telomerase	HalifaxProj (inhibit)		Telomerase is an enzyme that adds repetitive nucleotide sequences to the ends of chromosomes, known as telomeres. Telomeres protect the chromosome ends from deterioration or fusion with neighboring chromosomes. In most somatic (non-reproductive) cells, telomerase activity is low or absent, leading to gradual shortening of telomeres with each cell division. This shortening is associated with cellular aging and eventual cell senescence or apoptosis (programmed cell death). .
458-	testos	↑	testosterone			hormone therapy — slows cancer growth by lowering testosterone levels in the body. "shaking up prostate cancer with high-dose testosterone makes it more vulnerable to other treatments." there is a higher incidence of prostate cancer among men with low testosterone. https://www.smsna.org/patients/news/psa-and-total-testosterone-levels-in-men-with-prostate-cancer Prostate cancer is highly sensitive to androgenic stimulation. Testosterone—and more potently, its derivative dihydrotestosterone (DHT)—binds to the androgen receptor (AR) in prostate cells, which can drive the growth and survival of both normal and malignant cells. Castration-Resistant Prostate Cancer (CRPC): Even after testosterone levels are medically reduced, some prostate cancers continue to thrive by adapting their AR pathway. CRPC often signals a transition to a more aggressive, treatment-resistant state.
657-	TET1	↓	Ten-Eleven Translocation 1			TET1 (Ten-Eleven Translocation 1) is a gene that plays a crucial role in DNA demethylation and epigenetic regulation. TET1 is a member of the TET family of enzymes, which convert 5-methylcytosine (5-mC) to 5-hydroxymethylcytosine (5-hmC) in DNA. This process is essential for maintaining genome stability, regulating gene expression, and preventing tumorigenesis. TET1 is often downregulated or mutated, leading to decreased 5-hmC levels and aberrant DNA methylation patterns. This can result in the silencing of tumor suppressor genes and the activation of oncogenes, contributing to cancer development and progression.
303-	TET2	↓	tet oncogene family member 2	CGL-Driver Genes	TSG	TET2 (Ten-Eleven Translocation 2) is a gene that encodes an enzyme involved in the process of DNA demethylation, which is crucial for regulating gene expression and maintaining genomic stability. TET2 is a critical epigenetic regulator whose dysregulation—mainly through mutations—plays a significant role in the development and progression of various cancers, particularly in hematologic malignancies. Its impact on DNA methylation and subsequent gene expression changes makes it a key player in oncogenesis and a potential target for epigenetic therapies. The prognostic implications of TET2 mutations are context-dependent, contributing valuable information regarding disease progression, patient outcomes, and treatment response. Loss-of-function mutations or reduced activity of TET2 can lead to aberrant DNA methylation patterns, which may result in inappropriate gene silencing (including of tumor suppressor genes) or activation of oncogenes. This disruption in the normal epigenetic landscape contributes to the development and progression of various cancers, particularly hematological malignancies such as myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML).
887-	Tf	↑	Transferrin			Transferrin is a glycoprotein found in the blood that binds and transports iron throughout the body. Its primary role is to deliver iron to various tissues, especially to cells that require iron for processes like hemoglobin synthesis. Transferrin itself is a circulating protein primarily produced by the liver. Although its serum levels are clinically monitored (e.g., in iron studies and nutritional assessments), cancer-related studies more commonly focus on uptake mechanisms (via the transferrin receptor) rather than on changes in transferrin production per se. In some tumor microenvironments, local factors might influence transferrin levels, but the clinical focus tends to be on how cancer cells take up iron.
694-	TFAP2A	⇅	Transcription Factor AP-2 alpha		Transcription Factor	TFAP2A (Transcription Factor AP-2 alpha) is a transcription factor that plays a crucial role in various cellular processes, including cell growth, differentiation, and survival. In the context of cancer, TFAP2A has been implicated in both tumor suppression and oncogenesis, depending on the type of cancer and the cellular context. TFAP2A has been shown to act as a tumor suppressor in certain types of cancer, such as breast cancer, where it regulates the expression of genes involved in cell cycle arrest, apoptosis, and DNA repair. On the other hand, TFAP2A has also been implicated in the development and progression of other types of cancer, such as melanoma, where it promotes cell proliferation, survival, and metastasis. Transcription Factor AP-2 alpha (TFAP2A) is an important regulatory protein that plays multifaceted roles in normal development and cancer biology. Its impact on tumor progression and prognosis is complex, reflecting its ability to function as both a tumor suppressor and, in some contexts, as an oncogenic factor. Variations in its expression and activity across different cancers underscore its potential utility as a prognostic biomarker and a target for therapy.
1102-	TFEB	↑	Transcription Factor EB			TFEB is a member of the MiT/TFE (microphthalmia/transcription factor E) family and plays a crucial role in controlling the transcription of genes related to lysosome function and autophagy. • Its subcellular localization (cytosolic versus nuclear) is tightly regulated, with nuclear translocation being associated with transcriptional activation of target genes. TFEB is emerging as an important regulator in cancer biology, and its role as a prognostic marker is under active research. Its expression and activation state may offer insights into tumor behavior, especially regarding autophagy and metabolic adaptation. Overexpressed in RCC, Pca,
465-	TfR1/CD71	↑	Transferrin receptor protein 1,		gene/protein	also called CD71 a protein that in humans is encoded by the TFRC gene. A protein that mediates iron uptake from transferrin into cells. transferrin receptor, which can control iron metabolism, is frequently expressed in tumor cells. As is well known, TfR1 binds to iron-loaded transferrin and plays a pivotal role in cellular uptake of iron as well as ferritin sequesters and stores the cellular iron.
304-	TGF-β	↑	transforming growth factor-beta	HalifaxProj(inhibit) CGL-CS TCGA		Human malignancies frequently exhibit mutations in the TGF-β pathway, and overactivation of this system is linked to tumor growth by promoting angiogenesis and inhibiting the innate and adaptive antitumor immune responses. anti-inflammatory cytokine In normal tissues, TGF-β plays an essential role in cell cycle regulation, immune function, and tissue remodeling. - In early carcinogenesis, TGF-β typically acts as a tumor suppressor by inhibiting cell proliferation and inducing apoptosis. In advanced cancers, cells frequently become resistant to the growth-inhibitory effects of TGF-β. - TGF-β then switches roles and promotes tumor progression by stimulating epithelial-to-mesenchymal transition (EMT), cell invasion, metastasis, and immune evasion. Non-canonical (Smad-independent) pathways, such as MAPK, PI3K/Akt, and Rho signaling, also contribute to TGF-β-mediated responses. Elevated levels of TGF-β have been detected in many advanced-stage cancers, including breast, lung, colorectal, pancreatic, and prostate cancers.  - The switch from a tumor-suppressive to a tumor-promoting role is often associated with increased TGF-β production and activation in the tumor microenvironment. High TGF-β expression or signaling activity is frequently correlated with aggressive disease features, resistance to therapy, increased metastasis, and poorer overall survival in many cancer types.
1099-	TGF-β1	↑	Transforming Growth Factor-Beta 1			TGF-β1 is one of three TGF-β ligands (β1, β2, β3) that initiate the TGF-β signaling cascade. In the context of cancer, TGF-β1 plays a dual role: Tumor Suppressor in Early Stages: In normal and early-stage tumor cells, TGF-β1 typically inhibits cell proliferation, induces apoptosis, and maintains tissue homeostasis. Tumor Promoter in Advanced Stages: As cancer progresses, TGF-β1 often promotes epithelial-to-mesenchymal transition (EMT), enhances invasiveness, contributes to immune evasion, and fosters a pro-metastatic microenvironment. Role in Early Tumorigenesis: Acts as a tumor suppressor via growth arrest and apoptosis. Role in Advanced Cancers: Promotes EMT, invasion, metastasis, and immune suppression. Expression in Cancer Types: Increased in advanced/ aggressive tumors in many cancer types. Prognostic Implications Elevated TGF-β1: associated with poor prognosis in several cancers due to its pro-tumorigenic functions. Therapeutic Targeting Blocking TGF-β1 activity (via antibodies or ligand traps) to reduce its tumor-promoting actions.
1098-	TGFβR1	↑	transforming growth factor-beta receptor type I			TGFβR1 (transforming growth factor-beta receptor type I) is a key signaling receptor in the TGF-β pathway. This pathway is well known for its dual roles in cancer—it can act as a tumor suppressor in normal and early-stage malignant cells but may promote tumor progression and metastasis in later stages. Often overexpressed Increased expression correlates with aggressive behavior and reduced survival Tumor Suppressor Versus Promoter: Early Stages: TGF-β signaling, through receptors like TGFβR1, can inhibit cell proliferation and induce apoptosis; hence, loss or reduced signaling in early stages may contribute to tumor initiation. Advanced Stages: Many tumors hijack the TGF-β pathway to enhance invasive properties, suppress immune responses, and promote metastasis. In these situations, overexpression of TGFβR1 can contribute to a more aggressive phenotype.
305-	Th1 response	↓	T helper response	HalifaxProj(promote)		The Th1 (T helper 1) response is a crucial component of the immune system, particularly in the context of cell-mediated immunity. Th1 cells are a subset of CD4+ T cells that primarily produce cytokines such as interferon-gamma (IFN-γ), which activate macrophages and enhance the ability of the immune system to combat intracellular pathogens, including viruses and certain types of cancer cells. Increased infiltration of Th1 cells and a strong Th1 cytokine profile within tumors are often associated with better clinical outcomes in various cancers (including melanoma, colorectal, and ovarian cancers). A robust Th1 response is a critical component of effective antitumor immunity. Th1 cells and their signature cytokines (such as IFN-γ and IL-2) enhance the activation and proliferation of cytotoxic T cells, macrophages, and natural killer cells, thereby promoting immune-mediated tumor cell destruction. High infiltration of Th1 cells and a strong Th1 cytokine profile within the tumor microenvironment are generally associated with favorable prognostic outcomes and improved responses to immunotherapies.
1043-	Th17	⇅	T helper 17 (Th17) cells			Th17 cells are a distinct subset of CD4+ T helper cells characterized by their production of interleukin-17 (IL-17) family cytokines (most notably IL-17A and IL-17F), as well as other effector molecules like IL-21 and IL-22. These cells play a key role in mediating inflammatory responses and defending against extracellular pathogens, particularly fungi and bacteria. Th17 cells have been reported to exhibit both pro-tumor and anti-tumor properties:   – Anti-Tumor Effects: In some contexts, the pro-inflammatory cytokines produced by Th17 cells can enhance anti-tumor immunity by recruiting and activating other immune cells (e.g., cytotoxic T lymphocytes and natural killer cells).   – Pro-Tumor Effects: Conversely, chronic inflammation driven by Th17 cells may promote tumor progression by encouraging angiogenesis, suppressing effective anti-tumor immune responses, or by directly supporting tumor cell survival and metastasis.
787-	Th2	↑	Type 2 helper cell			Type 2 helper cell (Th2) pathway is a subset of the immune response that plays a crucial role in the regulation of inflammation, allergies, and parasitic infections. Key cytokines involved in the Th2 pathway: IL-4, IL-13, IL-5, IL-9 Elevated levels of certain Th2 cytokines (e.g., IL-10) can suppress cytotoxic T cell responses, thereby impairing effective antitumor immunity. In several cancers (such as ovarian, gastric, and certain breast cancers), high levels of Th2 cytokines or an increased Th2 cell infiltration have been observed.  - The relative balance between Th1 and Th2 responses is critical, with a Th2-skewed response often suggesting a shift away from effective cytotoxic antitumor immunity. A predominant Th2 environment is frequently linked to worse prognostic features, including enhanced tumor progression, increased metastasis, and reduced overall survival in some cancer types.
547-	THBS2	↑	thrombospondin 2 gene			THBS2 derived from specific subsets of Cancer-associated fibroblasts(CAFs), defined as THBS2 + CAFs, correlated with dismal prognosis and EMT(epithelial-mesenchymal transition) activity across various cancer types. Thrombospondin-2 (THBS2) is highly expressed in various tumors and participates in angiogenesis of various tumors by activating the PI3K/AKT signaling pathway.
1224-	Thiols	↑	Thiols			"Thiols" generally refer to compounds containing sulfhydryl (–SH) groups, with glutathione (GSH) being one of the most abundant and well-studied cellular thiols. Thiol groups play essential roles in maintaining redox balance, detoxifying reactive oxygen species (ROS), and modulating protein function via post-translational modifications. • Elevated levels of glutathione and related thiols have been associated with enhanced resistance to chemotherapy and radiation, as these treatments often work by inducing oxidative damage.
708-	TILs	↓	tumor-infiltrating lymphocytes (TILs)			Tumor-infiltrating lymphocytes (TILs) are a type of immune cell that infiltrates the tumor microenvironment. TILs are a heterogeneous population of lymphocytes, including T cells, B cells, and natural killer (NK) cells, that migrate into the tumor tissue. High levels of TILs in the tumor microenvironment are often correlated with better clinical outcomes, including improved survival rates and response to therapy.
710-	TIM-3	↑	T-cell immunoglobulin and mucin-domain containing-3		protein	TIM-3 is a protein that plays a crucial role in the regulation of the immune system. It is expressed on the surface of certain immune cells, including T cells and macrophages. TIM-3 has been identified as a potential biomarker and therapeutic target. TIM-3 is often overexpressed on the surface of tumor-infiltrating T cells and other immune cells in various types of cancer, including melanoma, lung cancer, and breast cancer. The overexpression of TIM-3 on immune cells in the tumor microenvironment can contribute to immune suppression and tumor progression. TIM-3 can bind to its ligand, galectin-9, which is expressed on the surface of tumor cells. This binding can lead to the inhibition of T-cell function and the promotion of T-cell exhaustion, allowing the tumor to evade immune surveillance.
307-	TIMP-1	↑	Tissue Inhibitor of Metalloproteinases-1			a protein that plays a role in the regulation of matrix metalloproteinases (MMPs), which are enzymes involved in the breakdown of the extracellular matrix. TIMP-1 is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. High levels of TIMP-1 have been associated with poor prognosis and increased risk of metastasis (cancer spread) in some cancers.
308-	TIMP-2	⇅	Tissue Inhibitor of Metalloproteinases-2			TIMP-2 has been shown to have distinct effects on cancer progression compared to TIMP-1. Research has suggested that TIMP-2 may have anti-tumor effects in certain types of cancer, including: • Inhibiting tumor growth: TIMP-2 has been shown to inhibit the growth of tumor cells in vitro and in vivo. High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers. High levels of TIMP-2 have been associated with better prognosis and improved survival in some cancers. High TIMP-2 expression: Breast, Lung, colorectal, Prostrate. Low TIMP-2 expression: Ovarian, Pancreatic, Gastric.
823-	TIMP3	?	tissue inhibitor of metalloproteinases-3			TIMP-3 has been shown to have tumor suppressor properties, as it inhibits the activity of MMPs, which are involved in tumor growth, invasion, and metastasis.
306-	TJ	⇅	Tight junctions	HalifaxProj(promote)		Tight junctions are specialized structures that form a barrier between epithelial cells, regulating the passage of substances between the cells and maintaining the integrity of tissue. They play a crucial role in maintaining cell polarity, tissue homeostasis, and the selective permeability of epithelial layers. 1.Overexpression of some claudins (e.g., claudin-1, -3, -4) in certain cancers is often associated with increased tumor aggressiveness and poor prognosis (protumor effects). 2.Downregulation or mislocalization of occludin and ZO proteins is generally linked to loss of cell–cell adhesion, EMT, and worse outcomes. 3.In contrast, loss of claudin-7 can remove its tumor suppressor functions, thereby facilitating invasion. The expression and impact of tight junction components in cancer is an area of active research—each protein can have dual roles (protumor or tumor suppressive) based on the tumor type, the molecular context, and the stage of disease progression.
1258-	TKT	↑	transketolase			Transketolase is a key enzyme in the non-oxidative arm of the pentose phosphate pathway (PPP), and alterations in its expression or activity can affect cellular metabolism, redox balance, and biosynthetic processes that are critical for rapidly proliferating cancer cells. – Role: TKT catalyzes the reversible transfer of two-carbon units between sugars in the non-oxidative PPP. – Impact: By contributing to the generation of ribose-5-phosphate for nucleotide synthesis and influencing the production of NADPH, TKT activity supports both biosynthetic demands and antioxidative defense in tumor cells. -Alterations in TKT expression can therefore impact the balance between ROS generation and detoxification, influencing cell survival and chemoresistance. -Inhibition of TKT may thus impair the cell’s antioxidative defenses, leading to a buildup of ROS. Elevated ROS can contribute to oxidative stress, damage cellular components, and in some contexts, even promote cell death. – Many studies have observed that TKT is upregulated in various malignancies, including lung, breast, colon, and liver cancers. – Association with Aggressiveness: Elevated TKT expression is often correlated with higher proliferation rates, enhanced anabolic activity, and worse clinical outcomes in some cancer types.
1041-	TLR1	⇅	Toll-Like Receptor 1			TLR1 is one of the Toll-like receptors (TLRs), a family of pattern recognition receptors that play a critical role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLR1 expression is not confined solely to immune cells; its expression has also been detected in various tumor cells as well as in the surrounding stroma. Aberrant expression or activation of TLR1 in the tumor microenvironment can influence both innate and adaptive immune responses within tumors. This modulation can have complex effects on tumor progression. Due to its dual role, TLR1 holds potential as both a prognostic biomarker and a therapeutic target.
1042-	TLR2	⇅	Toll-Like Receptor 2			TLR2 is a member of the Toll-like receptor (TLR) family, which plays a key role in the innate immune system by recognizing pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLR2 is unique in its ability to form heterodimers with other TLRs (such as TLR1 and TLR6) to broaden its ligand specificity. TLR2 is often described as having a “double-edged sword” role. On one side, stimulation of TLR2 can enhance the immune system’s ability to detect and destroy tumor cells. On the other side, persistent TLR2 signaling may lead to a pro-tumorigenic environment characterized by the secretion of growth factors, angiogenic signals, and immune suppressive cytokines that facilitate tumor progression.
559-	TLR4	?	Toll-like receptor 4			also called CD284 (cluster of differentiation 284) a key activator of the innate immune response and plays a central role in the fight against bacterial infections. Accumulating evidences demonstrated that the activation of TLR4 in tumor microenvironment can not only boost the anti-tumor immunity but also give rise to immune surveillance and tumor progression. "double-edged sword” role of TLR4 activation
1308-	TLS	?	Tumor lysis syndrome			Tumor Lysis Syndrome (TLS) is a potentially life-threatening oncologic emergency that occurs when a large number of tumor cells are rapidly lysed (destroyed), either spontaneously or in response to cancer treatment (especially chemotherapy), releasing their intracellular contents into the bloodstream. This sudden release can lead to metabolic disturbances and organ dysfunction. -A metabolic complication resulting from the rapid destruction of malignant cells, leading to the release of intracellular potassium, phosphate, and nucleic acids (which are metabolized into uric acid) into the bloodstream. These changes can result in hyperkalemia, hyperphosphatemia, hyperuricemia, and secondary hypocalcemia. Possible aids: Aggressive Hydration: -Initiate intravenous fluids (often normal saline) to maintain good renal perfusion and facilitate excretion of electrolytes and metabolites. Uric Acid Lowering Agents: Allopurinol: Inhibits xanthine oxidase, reducing the formation of uric acid. Typically started before chemotherapy. Rasburicase: An enzyme that converts uric acid to allantoin (a more soluble and easily excreted compound), useful in high-risk patients. https://www.cancertreatmentsresearch.com/tls/?highlight=Lysis https://pmc.ncbi.nlm.nih.gov/articles/PMC4017246/
693-	TNC	↑	tenascin-C		gene	The TNC gene, also known as tenascin-C, is a gene that encodes a protein involved in cell adhesion, migration, and signaling. Tenascin-C is a glycoprotein that is expressed in various tissues, including the nervous system, muscle, and connective tissue. TNC gene is overexpressed in various types of cancer, including breast, lung, colon, and brain cancer. The overexpression of tenascin-C has been associated with tumor progression, metastasis, and poor prognosis.
309-	TNF-α	↑	TNF-α	HalifaxProj (block)		Tumor Necrosis Factor-alpha (TNF-α) is a cytokine that plays a complex role in cancer biology. It is primarily produced by activated macrophages and is involved in systemic inflammation. TNF-α is a pro-inflammatory cytokine that can promote inflammation, which is a known factor in cancer development. Overall, the expression of TNF-α in cancers is often linked to inflammation, tumor progression, and the tumor microenvironment.
914-	TNF-β	↑	Tumor Necrosis Factor-beta			Tumor Necrosis Factor-beta (TNF-β), also known as Lymphotoxin-alpha (LT-α), is a cytokine involved in systemic inflammation and one of the cytokines that make up the tumor necrosis factor family. TNF-β is typically high expression in cancers with poor prognosis.
310-	TNFAIP3	↓	tumor necrosis factor, alpha-induced protein 3	CGL-Driver Genes	TSG	TNFAIP3, also known as A20, is a protein that plays a critical role in regulating immune responses and maintaining cellular homeostasis. It functions primarily as a negative regulator of the NF-κB signaling pathway, which is involved in inflammation, immune response, and cell survival. In certain solid tumors, such as some breast or colorectal cancers, the loss or silencing of TNFAIP3 may contribute to increased NF-κB activity, leading to a more aggressive phenotype
381-	TNFR 1	⇅	Tumor necrosis factor receptor 1,			TNFR-1 is an important member of the death receptor family that shares the capability of inducing apoptotic cell death. TNFR1 (p55): Often expressed ubiquitously, TNFR1 can mediate both apoptotic and survival signals. In some cancers, its upregulation has been associated with increased inflammatory signaling and may contribute to tumor progression through NF-κB activation.
1117-	TOP1	↑	Topoisomerase I			Topoisomerase I (TOP1) is an essential nuclear enzyme involved in relieving DNA supercoiling during replication and transcription. • Elevated TOP1 expression has been observed in several tumor types, such as colorectal, ovarian, breast, and lung cancers. • Increased TOP1 levels may correlate with higher proliferation rates, as actively dividing tumor cells require efficient relief of DNA • In some cancers, high TOP1 expression has been associated with aggressive tumor behavior, higher grade, and potentially poorer clinical outcomes. This may be due in part to increased proliferation and/or a greater propensity for genomic instability. • In other contexts, TOP1 expression might indicate sensitivity to TOP1-targeted therapies. For example, tumors with high TOP1 activity may respond better to chemotherapeutic agents (e.g., irinotecan) that target the enzyme, potentially improving outcomes when appropriate treatment is administered. TOP1 is a critical enzyme in maintaining DNA integrity whose expression in cancers can reflect tumor proliferation and genomic instability. While high TOP1 expression is often associated with aggressive tumor behavior and poorer prognosis in several cancer types, it also has therapeutic relevance because tumors with elevated TOP1 may be more sensitive to TOP1 inhibitors.
1321-	TOP2	↑	Topoisomerase II			Topoisomerase II (Top2) is a critical nuclear enzyme involved in managing the topology of DNA during essential cellular processes like replication, transcription, recombination, and chromosomal segregation. -rapidly dividing cells, including many cancer cells, often show higher Top2 expression. - In several cancers, such as breast, lung, and hematological malignancies, increased Top2 expression has been correlated with more aggressive tumor subtypes and poorer clinical outcomes. -The level of Top2 expression can sometimes be used as a prognostic marker, informing predictions about disease progression and potentially patient survival.
1113-	TOPflash	∅	TOPflash		reporter construct	TOPflash is not an endogenous gene or protein but rather a reporter construct that is widely used in experimental studies to assess the transcriptional activity of the canonical Wnt/β-catenin signaling pathway By comparing the activity of TOPflash with that of a control reporter (such as FOPflash, which contains mutated TCF binding sites), investigators assess the specific contribution of Wnt/β-catenin signaling in cancer cell lines or experimental models. Instead, the prognostic relevance lies in the fact that high activity of the canonical Wnt pathway—often inferred from assays using TOPflash—has been associated with more aggressive cancer phenotypes and poorer prognoses in several tumor types.
627-	TOS	↑	total oxidant status			Total oxidant status (TOS) refers to the overall level of oxidants in the body, which can be an important factor in cancer biology. Oxidative stress, resulting from an imbalance between oxidants and antioxidants, is implicated in cancer development, progression, and metastasis. Elevated TOS can lead to DNA damage, promote inflammation, and affect cell signaling pathways, all of which can contribute to tumorigenesis. Elevated TOS levels have been associated with poor prognosis in various cancers. Oxidative Stress Markers: Reactive Oxygen Species (ROS): Includes superoxide anions, hydrogen peroxide, and hydroxyl radicals. Malondialdehyde (MDA): A byproduct of lipid peroxidation, often used as a marker for oxidative stress. 8-Hydroxydeoxyguanosine (8-OHdG): A marker of oxidative DNA damage. Protein Carbonyls: Indicators of protein oxidation. 2. Antioxidant Defense Mechanisms: Superoxide Dismutase (SOD): Enzyme that catalyzes the dismutation of superoxide into oxygen and hydrogen peroxide. Catalase: Enzyme that converts hydrogen peroxide into water and oxygen. Glutathione Peroxidase (GPx): Reduces hydrogen peroxide and lipid peroxides. Glutathione (GSH): A major antioxidant that protects cells from oxidative stress.
1025-	toxicity	?	toxicity
311-	TP53	↓	tumor protein p53	CGL-Driver Genes	TSG	TP53 is a gene that encodes the p53 protein, which plays a crucial role in regulating the cell cycle, maintaining genomic stability, and preventing tumor formation. It is often referred to as the "guardian of the genome" due to its role in protecting cells from DNA damage and stress.
1285-	TPI	↑	Triosephosphate Isomerase			TPI (Triosephosphate Isomerase) – TPI is a key glycolytic enzyme that catalyzes the reversible interconversion of dihydroxyacetone phosphate (DHAP) and glyceraldehyde-3-phosphate (G3P). – By facilitating glycolysis, TPI plays a crucial role in energy production and metabolic flux in cells. – Enhanced Glycolytic Activity: Elevated TPI levels can correlate with increased glycolytic flux, supporting the energetic and biosynthetic demands of rapidly proliferating tumor cells. – Clinical Outcomes: Several studies have suggested that overexpression of TPI may be associated with more aggressive tumor behavior and poorer patient prognosis, though the specific prognostic value can be context- and cancer type–dependent.
596-	TPM4	↑	Tropomyosin 4			TPM4 is a protein that plays a crucial role in the regulation of cell shape, motility, and intracellular signaling. Research has shown that TPM4 is involved in various cellular processes, including cell proliferation, differentiation, and survival. In the context of cancer, TPM4 has been identified as a potential biomarker and therapeutic target. Studies have found that TPM4 is overexpressed in several types of cancer, including breast, lung, colon, and prostate cancer. The overexpression of TPM4 has been associated with cancer progression, metastasis, and poor patient outcomes.
312-	TRAF7	⇅	TNF receptor-associated factor 7	CGL-Driver Genes	TSG	TRAF7 (TNF Receptor Associated Factor 7) is a member of the TRAF family of proteins, which play critical roles in various cellular processes, including signal transduction, immune response, and apoptosis. TRAF7 is known to interact with various receptors and signaling pathways, including those related to tumor necrosis factor (TNF) and interleukin-1 (IL-1).
313-	TRAIL	↝	tumor necrosis factor-related apoptosis-inducing ligand			TRAIL (TNF-related apoptosis-inducing ligand) is a protein that plays a significant role in the regulation of apoptosis, or programmed cell death. It is part of the tumor necrosis factor (TNF) superfamily and has garnered interest in cancer research due to its ability to selectively induce apoptosis in cancer cells while sparing normal cells. TRAIL binds to specific receptors on the surface of cells, known as TRAIL receptors (TRAIL-R1 and TRAIL-R2), which triggers a cascade of signaling events leading to apoptosis. This selective action makes TRAIL a potential therapeutic agent for cancer treatment. TRAIL has been studied as a potential targeted therapy for various cancers, including breast, prostate, and lung cancer. Researchers are exploring ways to enhance its effectiveness, such as combining TRAIL with other treatments (chemotherapy, radiation) or using TRAIL in engineered forms (like TRAIL receptor agonists).
314-	TRAILR	↝	tumor necrosis factor-related apoptosis-inducing ligand receptor			TRAILR refers to TRAIL receptors, which are part of the signaling pathway activated by TNF-related apoptosis-inducing ligand (TRAIL). There are several TRAIL receptors, primarily classified into two categories: death receptors and decoy receptors. Types of TRAIL Receptors Death Receptors: TRAIL-R1 (also known as DR4): This receptor can initiate apoptosis when bound by TRAIL. It contains a death domain that activates downstream signaling pathways leading to cell death. TRAIL-R2 (also known as DR5): Similar to TRAIL-R1, TRAIL-R2 can also trigger apoptosis upon TRAIL binding. It is often considered more potent in inducing apoptosis compared to TRAIL-R1. Decoy Receptors: TRAIL-R3 (also known as DcR1): This receptor does not contain a death domain and cannot initiate apoptosis. Instead, it acts as a decoy, binding TRAIL and preventing it from activating the death receptors. TRAIL-R4 (also known as DcR2): Like TRAIL-R3, TRAIL-R4 also lacks a death domain and serves as a decoy receptor, inhibiting TRAIL-induced apoptosis.
315-	Trans Reg	↝	Transcriptional regulation	CGL-CF		Transcriptional regulation plays a crucial role in cancer development and progression. It involves the control of gene expression at the transcription level, which is essential for normal cellular functions, including cell growth, differentiation, and apoptosis.
316-	Treg lymp	↑	Treg lymphocytes	HalifaxProj(inhibit)		Regulatory T cells (Tregs) are a subset of T lymphocytes that play a crucial role in maintaining immune tolerance and preventing autoimmune diseases. They are characterized by the expression of specific markers, such as CD4, CD25, and the transcription factor FoxP3. Tregs are often found in high numbers within the tumor microenvironment. Their presence can suppress anti-tumor immune responses, allowing cancer cells to evade immune detection and destruction. By inhibiting the activity of effector T cells and other immune components, Tregs can promote tumor growth and metastasis.
673-	TregCell	↑	Treg cells			Treg cells, are a specific subtype of T cells that play a regulatory role in the immune system. They are also known as regulatory T cells or suppressor T cells. Treg cells are characterized by the expression of specific surface markers, such as CD4, CD25, and FOXP3, and are responsible for: -Suppressing excessive immune responses and preventing autoimmune diseases -Maintaining immune tolerance to self-antigens -Regulating the activity of other immune cells, such as effector T cells Treg cells are often found in the tumor microenvironment of various types of cancer High Tumor Levels: Breast, lung, CRC, Melanoma, ovarian, prostate, pancreatic.
536-	TREM-1	↑	triggering receptor expressed on myeloid cells-1			TREM1 promotes tumor progression, immunosuppression, and resistance to therapy by activating tumor-infiltrating myeloid cells. sTREM-1 Serum soluble triggering receptor expressed on myeloid cells-1. High levels of sTREM-1 were observed in 50% of breast cancer, 33.3% of Small Cell Lung carcinoma (SCLC), 26.7% of colorectal cancer and 13.3% of Non Small Cell Lung Carcinoma (NSCLC) patients.
510-	TRIB3	↑	tribbles homolog 3			TRIB3 overexpression is significantly linked to malignant progression and unfavorable prognosis in diverse solid tumors.
661-	TRIF	⇅	Toll/IL-1 receptor domain-containing adaptor-inducing interferon-β			TRIF (Toll/IL-1 receptor domain-containing adaptor-inducing interferon-β) is a protein that plays a crucial role in the innate immune response, particularly in the activation of interferons and the production of pro-inflammatory cytokines. Research has shown that TRIF is involved in the regulation of cancer development and progression. Here are some ways in which TRIF is linked to cancer: • Tumor suppression: TRIF has been shown to have tumor-suppressive effects in certain types of cancer, such as breast, lung, and colon cancer. It does this by activating interferons and other anti-tumor immune responses. Downregulated in: Breast, Lung, CRC Upregulated in: Melanoma, GBM
1254-	TrkB	↑	Tropomyosin receptor kinase B			Tropomyosin receptor kinase B (TrkB, encoded by the NTRK2 gene • TrkB is a high‐affinity receptor for brain-derived neurotrophic factor (BDNF) and neurotrophin-4 (NT-4). • It has been implicated in promoting cell survival, proliferation, migration, and resistance to apoptosis. • In several cancer types, increased TrkB expression has been associated with enhanced tumor aggressiveness and metastasis.
724-	Trop2	↑	Trop2			Trop2 is a cell surface glycoprotein that has been associated with various types of cancer. It is a member of the epithelial cell adhesion molecule (EpCAM) family and is involved in cell-cell adhesion, cell signaling, and cell migration. Overexpressed in: breast, lung, CRC, prostate Trop2 has also been identified as a potential biomarker for cancer diagnosis and prognosis. Trop2 expression are associated with poor prognosis and reduced overall survival in patients with various types of cancer.
883-	TRPM7	↑	transient receptor potential melastatin 7			TRPM7 (transient receptor potential melastatin 7) is a member of the TRP family of ion channels, which play a crucial role in various cellular processes, including cell growth, differentiation, and survival. High TRPM7 expression is associated with reduced overall survival in various types of cancer, including breast, lung, colon, prostate, ovarian, pancreatic, and glioblastoma.
1227-	TRPV1	⇅	transient receptor potential vanilloid 1			TRPV1 is a ligand-gated ion channel classically associated with nociception and heat sensation -TRPV1 is a nonselective cation channel that allows the influx of calcium (and other cations) when activated by various stimuli such as capsaicin, heat, or low pH. -TRPV1 can influence key cellular processes including proliferation, apoptosis, and migration by modulating intracellular calcium levels and downstream signaling cascades. -in some cases, TRPV1 activation can induce cell death, which might translate into less aggressive tumor behavior; however, this is not a universal finding. -TRPV1 is a non-selective cation channel, which is frequently overexpressed in highly malignant cancers -capsaicin may be able to induce cell death in urothelial cancer and glioma cells via TRPV1-dependent stimulation of excessive calcium (Ca2+) influx -activation of TRPV1 promotsd the generation of ROS - Variability in TRPV1 expression and function suggests that it might serve as one component of a broader prognostic panel rather than a standalone marker.
824-	TRX	↑	Thioredoxin		protein	Trx is a small protein that acts as a reducing agent, donating electrons to reduce oxidized proteins and other molecules. Trx is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. - cytosolic thioredoxin (TRX-1) and mitochondrial thioredoxin (TRX-2) -Thioredoxin is a pivotal redox regulator that protects cells from oxidative stress and supports survival and proliferation. -There is interest in combining thioredoxin inhibitors with conventional chemotherapy or radiotherapy to sensitize tumors to oxidative stress and improve treatment efficacy.
463-	TRX1	↑	Thioredoxin 1		serum marker BC	Trx1 is useful for the early diagnosis of breast cancer or the early prediction prognosis of breast cancer, and therefore has a valuable use as a diagnostic marker and companion marker to CEA and CA15-3 for breast cancer. - cytosolic thioredoxin (TRX-1) vs mitochondrial thioredoxin (TRX-2) The Trx1 level of patients with other types of cancer was close to that of women without cancer, indicating that the blood Trx1 level has potential to could discern BC from other types of cancer. Many tumor types, including lung, breast, colon, and prostate cancers, have shown elevated levels of TRX.
1218-	TRX2	↑	thioredoxin 2			Trx2 is an essential component of the mitochondrial thioredoxin system, working closely with thioredoxin reductase 2 (TrxR2) to reduce oxidized proteins and protect cells from oxidative stress. -mitochondrial thioredoxin (TRX-2) • By preserving mitochondrial integrity and regulating reactive oxygen species (ROS) levels, Trx2 contributes to cell survival, apoptosis regulation, and metabolic adaptation—all of which are critical in cancer biology. • Elevated levels of Trx2 may protect tumor cells against oxidative damage, potentially contributing to chemoresistance. -overexpression of Trx2 might be associated with more aggressive phenotypes and poorer clinical outcomes, although further studies are needed for definitive prognostic conclusions.
825-	TrxR	↑	Thioredoxin Reductase			TrxR is an enzyme that reduces Trx, allowing it to perform its reducing functions. It has been shown to have a role in cancer cell metabolism and survival. TrxR is overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer. -TrxR is a major antioxidant systems that maintains the intracellular redox homeostasis -inhibition causes an increase in ROS -TrxR inhibition leads to an increase in cellular oxidative stress and induces apoptosis TrxR inhibitors: -Piperlongumine -Withania somnifera (Ashwagandha) -Parthenolide -EGCG -Curcumin -Myricetin -Gambogic Acid
1207-	TrxR1	↑	thioredoxin reductase 1			TrxR1 or TXNRD1 (Thioredoxin Reductase 1) • Many studies have found that an elevated expression of TrxR1 in breast tumors, NSCLC, HCC correlates with increased tumor aggressiveness and a poorer prognosis. -TrxR1 expression was elevated by >50 fold in FaDu and HeLa cells, and by >20 fold in SCC-1 compared to either MSK-Leuk1 or keratinocytes • High TrxR1 levels have been associated with resistance to chemotherapy in some subtypes.
1222-	TrxR2	↑	thioredoxin reductase-mitochondrial			TrxR2 is a mitochondrial selenoprotein that reduces oxidized Trx2, thereby preserving a reduced environment within the mitochondria. • By maintaining mitochondrial redox homeostasis, TrxR2 contributes to cell survival, protects against oxidative stress, and helps regulate apoptosis. • Its activity is especially critical in rapidly proliferating cells, such as cancer cells, which often experience elevated levels of reactive oxygen species (ROS). -In various cancers—such as breast, lung, and colorectal cancers—upregulation of TrxR2 has been linked to enhanced cell survival, resistance to oxidative stress, and, in some studies, poorer clinical outcomes.
317-	trypsin	↑	trypsin			Trypsin is a serine protease enzyme that plays a crucial role in the digestive system by breaking down proteins into smaller peptides. Its primary function is in the small intestine, where it is activated from its precursor, trypsinogen, and helps in the digestion of dietary proteins. Research has demonstrated that abnormal expression of trypsinogen/trypsin can occur in various cancer types. Current research suggests that trypsin isoforms, particularly mesotrypsin (PRSS3), contribute to cancer progression through ECM degradation, activation of growth-promoting signals, and facilitation of metastasis. High expression levels have been associated with aggressive tumor behavior and poorer prognoses in various cancers.
1064-	TS	↑	thymidylate synthase			Thymidylate synthase (TS) is a key enzyme responsible for catalyzing the methylation of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a crucial step in the synthesis of thymidine—one of the four nucleotides required for DNA replication and repair. Due to its essential role in DNA synthesis, TS is a critical target for chemotherapeutic agents such as 5-fluorouracil (5-FU) and other antifolates. Many cancers exhibit elevated levels of TS expression compared to normal tissues. High TS expression can contribute to rapid cell proliferation and tumor growth by ensuring a sufficient supply of thymidine for DNA synthesis. Thymidylate synthase (TS) plays a central role in DNA synthesis and cell proliferation, making it a critical enzyme in cancer biology. Overexpression of TS is commonly observed in a range of tumor types and is associated with increased cellular proliferation, drug resistance, and generally poorer clinical outcomes. As both a therapeutic target and a prognostic marker, TS levels offer insight into tumor aggressiveness and potential responsiveness to chemotherapeutic agents.
318-	TSC1	↓	tuberous sclerosis 1	CGL-Driver Genes	TSG	The TSC1 gene, located on chromosome 9, encodes a protein called hamartin, which plays a crucial role in regulating cell growth and proliferation. Mutations in the TSC1 gene are associated with tuberous sclerosis complex (TSC), a genetic disorder characterized by the development of benign tumors in various organs. TSC1 (hamartin) and TSC2 (tuberin) form a complex that plays a critical role in regulating the mTOR (mechanistic target of rapamycin) pathway. • The TSC1/TSC2 complex acts as a negative regulator of mTOR signaling; when active, it helps suppress cell growth and proliferation. TSC1 and TSC2 serve as tumor suppressors TSC1 and TSC2 are not overexpressed in cancer; they are typically involved in loss-of-function scenarios that lead to tumorigenesis
497-	TSC2	↓	tuberous sclerosis complex (TSC)			TSC2 is a tumor suppressor gene as well as a disease-causing gene for autosomal dominant disorder tuberous sclerosis complex (TSC). TSC1 (hamartin) and TSC2 (tuberin) form a complex that plays a critical role in regulating the mTOR (mechanistic target of rapamycin) pathway. • The TSC1/TSC2 complex acts as a negative regulator of mTOR signaling; when active, it helps suppress cell growth and proliferation. TSC1 and TSC2 serve as tumor suppressors TSC1 and TSC2 are not overexpressed in cancer; they are typically involved in loss-of-function scenarios that lead to tumorigenesis
319-	TSHR	↓	thyroid stimulating hormone receptor	CGL-Driver Genes	Oncogene	The thyroid-stimulating hormone receptor (TSHR) is a G protein-coupled receptor that plays a crucial role in regulating thyroid function by mediating the effects of thyroid-stimulating hormone (TSH) on the thyroid gland. TSHR is primarily involved in the synthesis and release of thyroid hormones The TSHR gene encodes the thyroid-stimulating hormone receptor (TSHR), which is a G protein-coupled receptor located on the surface of thyroid follicular cells. This receptor is crucial for the regulation of thyroid hormone synthesis and secretion in response to thyroid-stimulating hormone (TSH), which is produced by the pituitary gland. TSHR expression is well established as a marker of differentiation and prognosis in thyroid cancer, with lower levels generally indicating a worse prognosis. more aggressive thyroid cancers (poorly differentiated or anaplastic thyroid carcinoma) may show reduced or lost TSHR expression, which is associated with a worse prognosis.
320-	TSP-1	↓	Thrombospondin-1			(TSP-1) is the first reported endogenous anti-angiogenic factor that can inhibit angiogenesis and tumorigenesis. Thrombospondin-1 (TSP-1) is a glycoprotein that plays a significant role in various biological processes, including cell adhesion, migration, and angiogenesis. It is part of the thrombospondin family of proteins and is known for its ability to regulate the formation of new blood vessels (angiogenesis) and modulate the immune response. TSP-1 is often considered a tumor suppressor because it can inhibit angiogenesis by binding to and activating certain receptors on endothelial cells, leading to reduced blood vessel formation. This can limit the supply of nutrients and oxygen to tumors, potentially inhibiting their growth.
321-	TumAuto	↓	Tumor autophagy	HalifaxProj(activate)		autophagy genes, including Atg3, Atg5, Atg6, Atg7, Atg10, Atg12, and Atg17. Tumor autophagy refers to the process by which cancer cells degrade and recycle cellular components through autophagy, a cellular mechanism that helps maintain homeostasis and respond to stress. Autophagy can have dual roles in cancer, acting as both a tumor suppressor and a promoter, depending on the context. Authophagy is the process used by cancer cells to “self-eat” to survive. Authophagy can be both good and bad. If authophagy is prolonged this will become a lethal process to cancer. On the other hand, for a short while (e.g. during chemotheraphy, radiotheraphy, etc.) authophagy is used by cancer cells to survive. For example, Chloroquine is a blocker of autophagy and has been used in a lab setting to dramatically enhance tumor response to radiotherapy, chemotherapy,
1265-	TumCA	↑	Tumor Cell adhesion
322-	TumCCA	↓	Tumor cell cycle arrest			Tumor cell cycle arrest refers to the process by which cancer cells stop progressing through the cell cycle, which is the series of phases that a cell goes through to divide and replicate. This arrest can occur at various checkpoints in the cell cycle, including the G1, S, G2, and M phases. S, G1, G2, and M are the four phases of mitosis
619-	TumCD	↓	Tumor Cell Death
323-	TumCG	↑	Tumor cell growth			Normal cells grow and divide in a regulated manner through the cell cycle, which consists of phases (G1, S, G2, and M). Cancer cells often bypass these regulatory mechanisms, leading to uncontrolled proliferation. This can result from mutations in genes that control the cell cycle, such as oncogenes (which promote cell division) and tumor suppressor genes (which inhibit cell division).
324-	TumCI	↑	Tumor Cell invasion			Tumor cell invasion is a critical process in cancer progression and metastasis, where cancer cells spread from the primary tumor to surrounding tissues and distant organs. This process involves several key steps and mechanisms: 1.Epithelial-Mesenchymal Transition (EMT): Many tumors originate from epithelial cells, which are typically organized in layers. During EMT, these cells lose their epithelial characteristics (such as cell-cell adhesion) and gain mesenchymal traits (such as increased motility). This transition is crucial for invasion. 2.Degradation of Extracellular Matrix (ECM): Tumor cells secrete enzymes, such as matrix metalloproteinases (MMPs), that degrade the ECM, allowing cancer cells to invade surrounding tissues. This degradation facilitates the movement of cancer cells through the tissue. 3.Cell Migration: Once the ECM is degraded, cancer cells can migrate. They often use various mechanisms, including amoeboid movement and mesenchymal migration, to move through the tissue. This migration is influenced by various signaling pathways and the tumor microenvironment. 4.Angiogenesis: As tumors grow, they require a blood supply to provide nutrients and oxygen. Tumor cells can stimulate the formation of new blood vessels (angiogenesis) through the release of growth factors like vascular endothelial growth factor (VEGF). This not only supports tumor growth but also provides a route for cancer cells to enter the bloodstream. 5.Invasion into Blood Vessels (Intravasation): Cancer cells can invade nearby blood vessels, allowing them to enter the circulatory system. This step is crucial for metastasis, as it enables cancer cells to travel to distant sites in the body. 6.Survival in Circulation: Once in the bloodstream, cancer cells must survive the immune response and the shear stress of blood flow. They can form clusters with platelets or other cells to evade detection. 7.Extravasation and Colonization: After traveling through the bloodstream, cancer cells can exit the circulation (extravasation) and invade new tissues. They may then establish secondary tumors (metastases) in distant organs. 8.Tumor Microenvironment: The surrounding microenvironment plays a significant role in tumor invasion. Factors such as immune cells, fibroblasts, and signaling molecules can either promote or inhibit invasion and metastasis.
325-	TumCM/A	↑	Tumor cell metabolism/acidosis	HalifaxProj(normalize)		Acidosis in the Tumor Microenvironment Lactic Acidosis: The increased glycolytic activity in tumors leads to the accumulation of lactic acid, resulting in a lower pH in the tumor microenvironment. This lactic acidosis can have several effects on tumor behavior and the surrounding tissue.
326-	TumCMig	↑	Tumor cell migration			Tumor cell migration is a critical process in cancer progression and metastasis, which is the spread of cancer cells from the primary tumor to distant sites in the body.
327-	TumCP	↑	Tumor Cell proliferation			Tumor cell proliferation is a key characteristic of cancer. It refers to the rapid and uncontrolled growth of cells that can lead to the formation of tumors.
897-	tumCV	↑	Cell Viability
604-	TumMeta	↑	Cancer Metastasis			Cancer metastasis is the process by which cancer cells spread from the original (primary) tumor to other parts of the body, forming new (secondary) tumors. This occurs when cancer cells invade surrounding tissues, enter the bloodstream or lymphatic system, and travel to distant organs or tissues.
328-	TumN	↓	Tumor necrosis	HalifaxProj(activate)		Tumor necrosis refers to the death of cells within a tumor, which can occur due to various factors, including insufficient blood supply (ischemia), lack of nutrients, or the effects of the immune response. Necrosis can lead to the breakdown of tumor tissue and may result in the release of cellular contents into the surrounding environment, which can provoke an inflammatory response.
329-	TumPF	↑	Tumor-promoting fibroblasts	HalifaxProj(deactivate)		Tumor-promoting fibroblasts, often referred to as cancer-associated fibroblasts (CAFs), play a significant role in the tumor microenvironment and contribute to cancer progression. CAFs are derived from various sources, including resident fibroblasts, mesenchymal stem cells, and even epithelial cells through a process called epithelial-to-mesenchymal transition (EMT). They exhibit distinct characteristics compared to normal fibroblasts, including altered gene expression and increased secretion of growth factors and cytokines.
330-	TumPInf	↑	Tumor-promoting inflammation	HalifaxProj(suppress)		Tumor-promoting inflammation is a critical area of research in cancer biology, as it highlights the complex interplay between the immune system and cancer development. Chronic inflammation can create an environment that supports tumor initiation, progression, and metastasis.
530-	TumVol	↑	Tumor Volume
915-	TumW	↑	Tumor Weight
1095-	TUNEL	⇅	Terminal deoxynucleotidyl transferase dUTP nick end labelin			The TUNEL (Terminal deoxynucleotidyl transferase dUTP nick end labeling) assay is widely used to detect DNA fragmentation associated with apoptosis. Rather than being a gene or protein whose expression is regulated, TUNEL is a methodological marker that reveals the extent of apoptosis within tumor tissues. TUNEL positivity is highly influenced by treatment. High apoptosis after chemotherapy or radiotherapy is generally viewed as a positive indicator of treatment effectiveness, whereas high basal apoptosis in untreated tumors can sometimes be associated with high tumor turnover and aggressiveness. Comprehensive analysis (often combining TUNEL with proliferation markers such as Ki-67) is needed for accurate prognostication.
421-	Twist	↑	Twist		transcription factor	Twist, the basic helix-loop-helix transcription factor, is involved in the process of epithelial to mesenchymal transitions (EMTs), which play an essential role in cancer metastasis. Overexpression of Twist or its promoter methylation is a common scenario in metastatic carcinomas. Twist is a key transcription factor for Epithelial-mesenchymal transition (EMT). Twist-1 overexpression was shown, recently, to be a factor of poor prognosis in melanomas Many studies use “TWIST” and “TWIST1” interchangeably (with TWIST1 being the canonical factor in humans Twist plays key roles in embryonic development and has been implicated in cancer progression, particularly through promoting epithelial-mesenchymal transition (EMT), invasion, and metastasis. TWIST1 directly represses epithelial markers (e.g., E-cadherin) while upregulating mesenchymal markers (e.g., N-cadherin, vimentin). Twist is most often upregulated in cancer cells compared to normal cells across multiple tumor types. – High Twist expression is consistently associated with aggressive clinical features, including increased invasiveness, metastasis, and reduced overall survival.
1028-	TXA2	↑	thromboxane A2			TXA2 is a bioactive lipid mediator primarily produced via the action of cyclooxygenases (COX-1/COX-2) and thromboxane synthase (TXA2S, gene TBXAS1), and it plays a role in regulating platelet aggregation, vasoconstriction, and cellular signaling that may contribute to tumor progression. TXA2 is a bioactive lipid mediator that, beyond its role in platelet aggregation and vascular regulation, is involved in several tumor-promoting processes such as inflammation, angiogenesis, and metastasis. In various cancers—such as breast, prostate, colorectal, lung, ovarian, and head and neck cancers—elevated TXA2 levels or enhanced signaling have been associated with more aggressive disease and poorer clinical outcomes.
1237-	TXNIP	↓	TBP-2			TXNIP {TBP-2 (Thioredoxin Binding Protein-2)} is broadly considered a tumor suppressor, given its roles in redox regulation, apoptosis, and cellular metabolism. -Thioredoxin‐interacting protein (TXNIP), which belongs to the arrestin family and is induced by various stimuli, interacts with and inhibits thioredoxin activity - lower TXNIP expression has been correlated with more aggressive disease features and poorer prognosis, while higher expression tends to associate with less aggressive phenotypes. -A consistent theme across these cancers is that lower TXNIP expression frequently correlates with more aggressive disease and a worse prognosis.
803-	Tyro3	↑	Tyro3		receptor tyrosine kinase	Tyro3 is a receptor tyrosine kinase that plays a crucial role in the regulation of cell growth, survival, and migration. Tyro3 is a member of the TAM (Tyro3, Axl, and Mer) family of receptors, which are involved in the regulation of various cellular processes, including cell growth, survival, and migration.
1160-	tyrosinase	↑	tyrosinase			tyrosinase expression has been evaluated in various cancers—primarily melanoma—and its association with prognosis. – Tyrosinase is normally expressed in melanocytes and is generally maintained in melanomas. – Elevated tyrosinase expression in blood (detectable tyrosinase mRNA) has been correlated with advanced disease stage and the presence of micrometastases.
331-	U2AF1	↑	U2 small nuclear RNA auxiliary factor 1	CGL-Driver Genes	Oncogene	U2 small nuclear RNA auxiliary factor 1 (U2AF1) is a protein that plays a crucial role in the splicing of pre-mRNA, which is an essential step in gene expression. It is part of the spliceosome complex, which is responsible for removing introns from pre-mRNA and joining exons together to form mature mRNA Mutant U2AF1 contributes to a protumor phenotype by misregulating alternative splicing, potentially leading to the production of aberrant protein isoforms that disrupt normal cell differentiation and promote survival and proliferation.
391-	UBE2C	↑	Ubiquitin-conjugating enzyme E2 C		protein/gene	Ubiquitin-conjugating enzyme E2 C is a protein that in humans is encoded by the UBE2C gene. UBE2C is upregulated in 28 different cancers. UBE2C expression is significantly higher in late-stage tumors. Silencing UBE2C arrests cell cycle progression at the G 1 /S phases, inhibits cell proliferation in pancreatic ductal adenocarcinoma and blocks the G 2 /M transition in melanoma . UBE2C is most frequently overexpressed in a wide array of cancers compared to their normal tissue counterparts. – High UBE2C expression is consistently associated with aggressive tumor features, advanced disease, and reduced overall survival.
553-	UCP1	↑	mitochondrial uncoupling protein 1			UCP1 for example has been shown to be expressed in prostate cancer and be related to a metastatic phenotype UCP1 and UCP3 are overexpressed in a large subgroup of non-small cell lung tumors and their expression coincides with increased glucose absorption, intensified glycolysis, and anaerobic glucose usage. UCP1 was negatively regulated to the process of TNBC. Overexpression of UCP1 could impair the malignant behavior of triple-negative breast cancer. UCP1 was down-regulated in colorectal cancer while positively related to a better prognosis UCP1 is a mitochondrial inner membrane protein most notably expressed in brown adipose tissue, where it uncouples oxidative phosphorylation to produce heat rather than ATP. – In cancer cachexia, increased UCP1 expression is linked to higher energy dissipation, contributing to weight loss and weakness, which can indirectly influence patient prognosis
1250-	UHRF1	↑	Ubiquitin-like with PHD and RING Finger domains 1			UHRF1 (Ubiquitin-like with PHD and RING Finger domains 1) is an epigenetic regulator known to be overexpressed in several cancer types. Its altered expression is often associated with poor prognosis. -UHRF1 is critical for the maintenance of DNA methylation during replication by recruiting DNA methyltransferase 1 (DNMT1) to hemimethylated DNA. -Evidence suggests that UHRF1 can negatively regulate p53, a key tumor suppressor protein. -Several studies have linked high UHRF1 expression with the activation of the PI3K/AKT pathway.
428-	uPA	↑	Urokinase plasminogen activator			uPA (urokinase plasminogen activator) is a serine protease that plays a crucial role in the conversion of plasminogen to plasmin, an enzyme responsible for degrading various components of the extracellular matrix (ECM). This activity is central to processes such as tissue remodeling, cell migration, and angiogenesis. In the context of cancer, uPA facilitates tumor invasion and metastasis by promoting ECM degradation, while its interaction with its receptor (uPAR) and inhibitors (such as PAI-1) forms a regulatory axis that is frequently dysregulated in malignancies. Patients with higher pretreatment serum uPA (≥1 ng/ml) had significantly shorter OS Elevated uPA expression has been observed in a broad range of cancers, including breast, colorectal, lung, and prostate cancers. These high levels are often indicative of increased proteolytic activity within the tumor microenvironment. Tumors with aggressive behavior often exhibit upregulation of uPA, along with its receptor uPAR. This upregulation enhances plasmin generation and leads to an environment conducive to invasion and metastasis. Elevated uPA levels in tumor tissues have been strongly associated with poor clinical outcomes. High uPA expression is correlated with increased risk of metastasis, higher likelihood of recurrence, and reduced overall survival in several cancer types.
429-	uPAR	↑	Urokinase-type plasminogen activator receptor			uPAR is a target for the treatment of cancer, because it is expressed at low levels in healthy tissues but at high levels in malignant tumours. uPAR is typically overexpressed in breast cancer tissues relative to normal breast epithelium. • Prognosis: – High uPAR levels correlate with increased invasiveness, higher grades, and an overall poorer prognosis. • Function: – uPAR contributes to tumor cell migration and invasion, supporting a protumor role. uPAR is considered protumor because its overexpression facilitates extracellular matrix degradation, enhances cell migration/invasion, and supports signaling pathways that promote tumor progression.
459-	UPR	↑	Unfolded Protein Response			cellular stress response related to the endoplasmic reticulum (ER) stress, which involves protein folding, quality control, and signaling pathways. The unfolded protein response (UPR) is the cells' way of maintaining the balance of protein folding in the endoplasmic reticulum. (UPR) is triggered by the presence of misfolded proteins in the endoplasmic reticulum. The UPR is a cellular stress response activated by the accumulation of unfolded or misfolded proteins in the endoplasmic reticulum (ER). - It is primarily mediated by three ER-resident sensors: IRE1α, PERK, and ATF6. Cancer cells often experience high levels of protein synthesis, hypoxia, nutrient deprivation, and oxidative stress, all of which can activate the UPR. – Numerous studies have reported that key UPR components (e.g., GRP78/BiP, IRE1α, PERK, CHOP) are overexpressed in various malignancies such as breast, pancreatic, lung, and prostate cancers. Unfolded Protein Response is typically upregulated in cancers and is associated with poorer prognosis due to its role in promoting cell survival, adaptation to stress, and therapeutic resistance. Although the UPR harbors the potential for tumor-suppressive (apoptotic) effects under severe stress conditions, its predominant activation in tumors supports an adaptive, protumorigenic state that facilitates cancer progression. Targeting UPR components and modulating this balance remain promising therapeutic strategies.
1322-	uricA	↑	uric acid			Uric acid is a bit of a double-edged sword when it comes to oxidative stress: Antioxidant Effects: -Uric acid is considered one of the most important antioxidants in human plasma. It can scavenge reactive oxygen species (ROS) such as singlet oxygen and peroxyl radicals. -Its antioxidant properties help protect cells and tissues from oxidative damage, contributing to the overall antioxidant capacity of the blood. Pro-oxidant Effects: -Under certain conditions, especially at high concentrations, uric acid can also act as a pro-oxidant. For example, it may promote inflammation and oxidative stress in vascular tissues, which has been associated with conditions like hypertension and cardiovascular disease. -The formation of monosodium urate crystals (as seen in gout) is linked to inflammatory reactions, and these crystals can contribute to local oxidative stress. -Some studies have reported that elevated serum uric acid levels can be found in patients with certain cancers, possibly reflecting high cell turnover or altered metabolism. In some cases, higher local concentrations of uric acid might contribute to the antioxidant environment or even affect inflammatory processes.
1180-	UrinaryC	↓	urinary continence			Ability to hold urine in from leaking.
332-	UroPA	↑	Urokinase plasminogen activator	HalifaxProj (suppress)		Urokinase plasminogen activator (uPA) is an enzyme that plays a significant role in the process of fibrinolysis, which is the breakdown of fibrin in blood clots. It is involved in the conversion of plasminogen to plasmin, leading to the degradation of fibrin and other components of the extracellular matrix. This process is crucial in various physiological and pathological conditions, including wound healing and tissue remodeling. Elevated levels of uPA and uPAR in tumor tissues and bodily fluids (such as serum) have been associated with a poor prognosis in several types of cancer, including breast, ovarian, and colorectal cancers. The rationale is that increased uPA activity can facilitate tumor cell invasion through the degradation of the extracellular matrix, allowing cancer cells to spread to other tissues.
648-	USF1	↑	Upstream transcription factor 1			Upstream transcription factor 1 (USF1) is a protein that plays a crucial role in the regulation of gene expression. USF1 overexpression was found to promote cell proliferation and tumor growth in breast cancer. USF1 was overexpressed in lung cancer tissues and cell lines.
420-	VCAM-1	↑	Vascular cell adhesion protein 1			a protein that in humans is encoded by the VCAM1 gene. VCAM-1 is a cell surface glycoprotein primarily expressed by activated endothelial cells. It mediates adhesion of leukocytes and plays a key role in inflammation and immune cell trafficking. In the tumor microenvironment, VCAM-1 is often upregulated and is involved in the interactions between tumor cells, immune cells, and the vasculature. VCAM-1 is predominantly protumorigenic in cancer contexts. Its upregulation in tumor tissues and vasculature contributes to enhanced tumor cell adhesion, migration, and metastasis, and correlates with poor clinical outcomes
1111-	VDR	↓	Vitamin D receptor			Vitamin D receptor -higher VDR expression in breast tumors is associated with a better prognosis. - In colorectal cancer, reduced VDR expression has been frequently linked to more advanced disease and poorer outcomes. -VDR expression can inhibit prostate cancer cell growth by slowing proliferation and promoting differentiation.
334-	VEGF	↑	Vascular endothelial growth factor	HalifaxProj (inhibit)		a signal protein produced by many cells that stimulates the formation of blood vessels. Vascular endothelial growth factor (VEGF) is a signal protein that plays a crucial role in angiogenesis, the process by which new blood vessels form from existing ones. This process is vital for normal physiological functions, such as wound healing and the menstrual cycle, but it is also a key factor in the growth and spread of tumors in cancer. Because of its significant role in tumor growth and progression, VEGF has become a target for cancer therapies. Anti-VEGF therapies, such as monoclonal antibodies (e.g., bevacizumab) and small molecule inhibitors, aim to inhibit the action of VEGF, thereby reducing blood supply to tumors and limiting their growth. These therapies have been used in various types of cancer, including colorectal, lung, and breast cancer.
768-	VEGFR2	↑	Vascular Endothelial Growth Factor Receptor 2		receptor tyrosine kinase	VEGFR2 is a receptor tyrosine kinase that plays a crucial role in angiogenesis, the process of new blood vessel formation. In cancer, VEGFR2 is often overexpressed, promoting the growth of new blood vessels that supply the tumor with oxygen and nutrients, facilitating its growth and metastasis. Inhibiting VEGFR2 signaling has been shown to be an effective strategy in cancer therapy, and several VEGFR2 inhibitors have been approved for the treatment of various types of cancer, including renal cell carcinoma, colorectal cancer, and non-small cell lung cancer. These inhibitors work by blocking the binding of VEGF to VEGFR2, thereby inhibiting angiogenesis and tumor growth.
758-	VGCC	↑	Voltage-gated calcium channels		transmembrane proteins	VGCCs play a crucial role in various cellular processes, including cell signaling, proliferation, and differentiation. VGCCs are transmembrane proteins that regulate the influx of calcium ions into cells. Calcium ions act as a second messenger, triggering various signaling pathways that control cell growth, survival, and migration. In cancer cells, VGCCs can be overexpressed or mutated, leading to aberrant calcium signaling and contributing to tumor growth and metastasis. Overexpressed in: breast cancer, prostate cancer, colorectal cancer, glioblastoma Associated with: tumor growth, metastasis, and poor prognosis
335-	VHL	↓	von Hippel-Lindau tumor suppressor	CGL-Driver Genes	TSG	The von Hippel-Lindau (VHL) tumor suppressor gene is a critical gene involved in the regulation of cell growth and response to oxygen levels in the body. In low oxygen conditions (hypoxia), the VHL protein is less active, allowing HIFs to accumulate and activate the transcription of genes that promote angiogenesis (formation of new blood vessels), erythropoiesis (production of red blood cells), and metabolic adaptation.
336-	Vim	↑	Vimentin			Vimentin, a major constituent of the intermediate filament family of proteins, is ubiquitously expressed in normal mesenchymal cells and is known to maintain cellular integrity and provide resistance against stress. Vimentin is overexpressed in various epithelial cancers, including prostate cancer, gastrointestinal tumors, tumors of the central nervous system, breast cancer, malignant melanoma, and lung cancer. Vimentin’s overexpression in cancer correlates well with accelerated tumor growth, invasion, and poor prognosis; however, the role of vimentin in cancer progression remains obscure. In many epithelial-derived tumors (carcinomas), elevated Vimentin expression is often observed in cancer cells that have undergone EMT. This upregulation is characteristic of a shift toward a mesenchymal state, which is associated with reduced cell–cell adhesion and increased motility. Vimentin expression is also noted in the tumor stroma, reflecting the presence and activation of mesenchymal cells such as cancer-associated fibroblasts (CAFs). This dual expression can contribute to the remodeling of the tumor microenvironment. The degree of Vimentin expression may vary depending on the tumor type, grade, and stage. More aggressive and advanced tumors tend to show higher levels of Vimentin expression. High Vimentin expression has been correlated with poor clinical outcomes in several cancers, including breast, colorectal, prostate, and lung cancers. Elevated Vimentin levels are typically associated with higher tumor grade, increased invasiveness, enhanced metastatic potential, and a greater risk of recurrence. As a component of the EMT signature, high Vimentin expression can serve as an indicator of a more aggressive tumor phenotype and is often associated with reduced overall survival.
337-	vinculin	⇅	vinculin			A strong association between vinculin gene amplification and advanced prostate cancers has been documented, and knockdown of vinculin expression has been shown to reduce the growth of PC-3 cells, demonstrating that vinculin is a tumor-promoting protein It plays a critical role in linking the actin cytoskeleton to cell membrane adhesion complexes, thereby regulating cell shape, adhesion, and motility. The level of vinculin expression can differ between early-stage and advanced tumors. Some studies suggest that vinculin loss may facilitate epithelial–mesenchymal transition (EMT) and distant metastasis.  – Conversely, certain contexts document elevated vinculin expression that may support the dynamic cellular processes required for migration or survival in a specific microenvironment vinculin is generally linked to a tumor-suppressive function in the context of cancer by maintaining cell–cell and cell–ECM adhesions. Altered expression or mislocalization of vinculin can lead to a loss of cell adhesion, increased migration, and enhanced invasiveness, factors that correlate with poorer clinical prognosis.
1253-	VitC	?	Vitamin C levels			Adequate intracellular vitamin C can contribute to the hydroxylation and subsequent degradation of HIF-1α. Elevated HIF-1α is often associated with aggressive tumor behavior and poor prognosis. Ascorbate Transporters • SVCT2 (Sodium-Dependent Vitamin C Transporter 2) – Role: Mediates the uptake of ascorbate into cells. • GLUT Transporters (e.g., GLUT1) – Role: While primarily known for transporting glucose, certain GLUT family members (especially GLUT1) also facilitate the uptake of the oxidized form of vitamin C (dehydroascorbate).
851-	VitD	↓	Vitamin D			Vitamin D expression is decreased in: Breast, CRC, Prostate, Lung, Melanoma, GBM, Pancreatic cancer. (Poor prognosis, with decreased overall survival) Vitamin D expression is increased in RCC, Thyroid, Ovarian, Endometrial, Cervical cancers (***Better prognosis, with increased overall survival) See VDR and CYP27B1 CYP27B1 is the enzyme responsible for converting 25‐hydroxyvitamin D into its active form, 1,25‐dihydroxyvitamin D (calcitriol). As with VDR, CYP27B1 expression in tumors has been investigated for its potential prognostic significance in various cancers.
1252-	VitE	?	Vitamin E levels			Vitamin E is best known for its ability to neutralize free radicals and reduce oxidative damage to lipids, proteins, and DNA. • α‐Tocopherol Transfer Protein (TTPA) – Role: Transfers vitamin E (α‐tocopherol) between membranes.
1296-	VM	↑	vasculogenic mimicry			vasculogenic mimicry (VM) -Vasculogenic mimicry refers to the process by which aggressive tumor cells form vascular channel–like structures independently of endothelial cells. -Unlike classical angiogenesis where new blood vessels develop from preexisting vasculature, VM involves tumor cell plasticity that allows cancer cells to create perfusable networks resembling blood vessels. -This phenomenon is often observed in highly aggressive and metastatic tumors, reflecting the ability of these cells to adapt to hypoxia and other microenvironmental stresses. -Tumor regions with low oxygen levels often stimulate VM formation as an adaptive response. Hypoxia promotes a switch in cellular metabolism and gene expression that supports both angiogenesis and vasculogenic mimicry, thus ensuring continued nutrient supply and waste removal.
947-	Warburg	↑	Warburg Effect		effect	The Warburg effect is a metabolic phenomenon in which cancer cells preferentially use glycolysis for energy production, even in the presence of oxygen. Targeting the pathways involved in the Warburg effect is a promising strategy for cancer treatment. Warburg effect (GLUT1, LDHA, HK2, and PKM2) Here are some of the key pathways and potential targets: Note: use database Filter to find inhibitors: Ex pick target HIF1α, and effect direction ↓ 1.Glycolysis Inhibitors:(2-DG, 3-BP) -HK2 Inhibitors: such as 2-deoxyglucose, can reduce glycolysis -PFK1 Inhibitors: such as PFK-158, can reduce glycolysis -PFKFB Inhibitors: -PKM2 Inhibitors: (Shikonin) -can reduce glycolysis -LDH Inhibitors: (Gossypol, FX11) -reducing the conversion of pyruvate to lactate. -inhibiting the production of ATP and NADH. -GLUT1 Inhibitors: (phloretin, WZB117) -a key transporter involved in glucose uptake. -GLUT3 Inhibitors: -PDK1 Inhibitors: (dichloroacetate) - a key enzyme involved in the regulation of glycolysis. 2.Gluconeogenesis pathway: -FBP1 Activators: can increase gluconeogenesis -PEPCK1 Inhibitors: can reduce gluconeogenesis 3.Pentose phosphate pathway: -G6PD Inhibitors: can reduce the pentose phosphate pathway 4.Mitochondrial metabolism: -MPC1 Inhibitors: can reduce mitochondrial metabolism and inhibit cancer -SDH Inhibitors: can reduce mitochondrial metabolism and inhibit cancer cell growth. 5.Hypoxia-inducible factor 1 alpha (HIF1α) pathway: -HIF1α inhibitors: (PX-478,Shikonin) -reduce expression of glycolytic genes and inhibit cancer cell growth. 6.AMP-activated protein kinase (AMPK) pathway: -AMPK activators: (metformin,AICAR,berberine) -can increase AMPK activity and inhibit cancer cell growth. 7.mTOR pathway: -mTOR inhibitors:(rapamycin,everolimus) -can reduce mTOR activity and inhibit cancer cell growth.
603-	Weight	↓	Weight
1181-	Wmax	↓	Wmax			Wmax typically refers to the maximal power output a person can generate during an exercise test. In exercise physiology, it's often measured in watts and provides insight into an individual's aerobic fitness and muscular strength. When it comes to cancer—specifically in oncology and exercise research—Wmax is used as an objective measure to assess a patient's physical capacity and response to exercise interventions.
377-	Wnt	↑	Wingless-related integration site			The Wnt signaling pathway is a complex network of proteins that plays a crucial role in various cellular processes, including cell proliferation, differentiation, and migration. It is particularly important during embryonic development and tissue homeostasis. Dysregulation of the Wnt pathway has been implicated in various cancers, making it a significant area of research in oncology. Wnt Ligands Wnt1: Often overexpressed in breast cancer and some types of leukemia. Wnt Receptors Frizzled (Fzd) Receptors: Different Fzd receptors (e.g., Fzd1, Fzd2, Fzd7) have been implicated in various cancers: Fzd1: Overexpressed in colorectal cancer. Fzd2: Associated with breast cancer and prostate cancer. Fzd7: Linked to gastric cancer and glioblastoma
338-	Wnt/(β-catenin)	↑	Wnt/(β-catenin)	HalifaxProj (inhibit) TCGA		The Wnt signaling pathway is activated when Wnt proteins bind to Frizzled receptors on the cell surface, leading to the stabilization and accumulation of β-catenin in the cytoplasm and its subsequent translocation to the nucleus. In the nucleus, β-catenin interacts with transcription factors to activate target genes that promote cell growth and survival.
339-	WT1	↑	Wilms tumor 1	CGL-Driver Genes	TSG	The Wilms tumor 1 (WT1) gene is a critical gene associated with the development of Wilms tumor, a type of kidney cancer that primarily affects children. WT1 is highly expressed in many solid tumors (such as ovarian, breast, lung, and colorectal cancers) as well as hematologic malignancies (e.g., acute leukemias). WT1 is generally overexpressed in many cancers and is associated with aggressive tumor behavior and poorer prognosis in several contexts. Its multifunctional nature, marked by its ability to act as both a transcriptional activator and repressor, underlies its complex role in tumorigenesis.
631-	XBP-1	↑	X-box binding protein 1			XBP-1 (X-box binding protein 1) is a transcription factor that plays a crucial role in the unfolded protein response (UPR). XBP-1 is activated in response to endoplasmic reticulum (ER) stress, which occurs when the ER is overwhelmed with unfolded or misfolded proteins. XBP-1 has been shown to have both tumor-promoting and tumor-suppressing roles. XBP-1 is overexpressed in various types of cancer, including breast, lung, colon, and pancreatic cancer. In some cases, XBP-1 overexpression has been associated with poor prognosis and reduced survival rates. Targeting XBP-1 and the UPR has been proposed as a potential therapeutic strategy for cancer treatment. Inhibitors of XBP-1 or other UPR components may be able to selectively kill cancer cells that are under ER stress, while sparing normal cells.
801-	xCT	↑	SLC7A11		protein	SLC7A11 (also known as xCT) xenobiotic transporter XCT (xenobiotic transporter) is a protein that plays a crucial role in the transport of xenobiotics, including chemotherapeutic agents, across cell membranes. xCT overexpressed in: breast, lung, colon, prostate, GBM, Pancreatic (with poor prognosis) Cancer cells often experience high levels of oxidative stress; upregulation of SLC7A11 helps to counteract this stress and supports cell survival. targeting SLC7A11 can sensitize tumor cells to oxidative damage and ferroptosis, offering a potential therapeutic avenue. SLC7A11 encodes the light chain subunit of the cystine/glutamate antiporter system X_c⁻. This transporter imports cystine into the cell and exports glutamate out. The imported cystine is then used to synthesize glutathione (GSH), a major antioxidant that helps control intracellular ROS levels. Many cancer cells experience elevated oxidative stress due to increased metabolic activity and stress conditions within the tumor microenvironment. Upregulation of SLC7A11 can provide a survival advantage by boosting GSH synthesis, thereby neutralizing ROS and preventing oxidative damage. High SLC7A11 activity helps prevent ferroptosis by ensuring continuous glutathione production. Glutathione is a cofactor for glutathione peroxidase 4 (GPX4), a key enzyme that detoxifies lipid peroxides. Mechanism: When SLC7A11 is inhibited, cystine uptake is reduced. This leads to glutathione depletion, compromised GPX4 activity, and eventually the accumulation of lipid peroxides that trigger ferroptosis. Inducing ferroptosis has become a promising anticancer strategy. Inhibitors targeting SLC7A11 (or related pathways) can lower glutathione levels, increasing susceptibility to ferroptotic cell death. This is especially attractive in cancers with high SLC7A11 expression, where blocking its function may selectively induce ferroptosis and overcome drug resistance.
396-	XIAP	↑	X-linked inhibitor of apoptosis protein (XIAP) baculoviral IAP repeat-containing protein 4 (BIRC4)			also known as BIRC4. XIAP is inhibited by DIABLO (Smac) and HTRA2 (Omi), two death-signaling proteins released into the cytoplasm by the mitochondria. High proportions of XIAP may function as a tumor marker. In developing prostate cancer, XIAP is one of four IAPs overexpressed in the prostatic epithelium XIAP functions predominantly as a protumorigenic protein in the context of cancer. Its upregulation is commonly observed in various tumor types and is associated with poor patient outcomes and resistance to therapy due to its potent inhibition of apoptosis.
940-	XIST	↑	X-inactive specific transcript			XIST (X-inactive specific transcript) is a long non-coding RNA that plays a crucial role in X-chromosome inactivation in females. However, XIST has also been implicated in various types of cancer, where it can be expressed in both males and females. XIST is typically overexpressed in cancers, and associated with poor prognosis
340-	YAP/TEAD	↑	YAP/TEAD activity	HalifaxProj (inhibit)		YAP (Yes-associated protein) and TEAD (TEA domain transcription factors) are key components of the Hippo signaling pathway, which plays a crucial role in regulating cell growth, proliferation, and apoptosis. Activation of YAP: In normal conditions, the Hippo pathway inhibits YAP activity, preventing excessive cell growth. However, when the Hippo pathway is inactivated (due to mutations or other factors), YAP becomes activated. This leads to increased cell proliferation and survival, contributing to tumorigenesis. TEAD as a Transcription Factor: YAP interacts with TEAD proteins to drive the expression of target genes that promote cell growth and inhibit apoptosis. This YAP/TEAD complex is often found to be overactive in several types of cancer, including liver, breast, and lung cancers.
836-	YMcells	↓	YOUNG’S MODULUS cancer cells			Young's modulus is a measure of the stiffness of a material. Cancer cells are often found to be softer and more deformable than normal cells, which can affect their ability to migrate and invade surrounding tissues. Young's modulus of breast cancer cells was significantly lower than that of normal breast cells. Another study found that the Young's modulus of ovarian cancer cells was lower than that of normal ovarian cells.
505-	ZBTB10	↓	ZBTB transcription Factor 10			ZBTB10, which was an important target of miR-27a, suppressed the expression of vascular endothelial growth factor (VEGF), VEGF receptor 1 (VEGFR1), VEGFR2 and survivin which were responsible for angiogenesis and metastasis of cancer. Downregulation of ZBTB10 has been noted in contexts where high miR-27a expression suppresses its levels, indirectly leading to the upregulation of genes that promote tumor progression. Lower levels of ZBTB10 have been associated in some studies with more aggressive tumor behavior and poorer prognosis. – The rationale is that reduced ZBTB10 expression may lead to unchecked Sp1 activity, driving the expression of pro-tumorigenic genes involved in proliferation, angiogenesis, and survival. Current evidence suggests that ZBTB10 may function as a tumor suppressor by inhibiting Sp1-dependent oncogenic pathways. In several cancers, reduced expression of ZBTB10—often driven by microRNA-mediated repression—correlates with enhanced tumor progression and poorer outcomes.
341-	Zeb1	↑	Zinc finger E-box-binding homeobox 1		protein	transcription factor that promotes tumor invasion and metastasis by inducing epithelial-mesenchymal transition (EMT) in carcinoma cells Zinc finger E-box-binding homeobox 1 (ZEB1) is a transcription factor that plays a significant role in various biological processes, including embryonic development, cell differentiation, and epithelial-to-mesenchymal transition (EMT). By repressing epithelial markers (e.g., E-cadherin) and promoting mesenchymal genes, Zeb1 facilitates cell migration, invasion, and metastasis. cancers (such as breast, colorectal, pancreatic, and lung cancers), Zeb1 is frequently upregulated. Zeb1 may be more prominent in specific tumor regions (e.g., invasive fronts) where EMT is actively occurring. High levels of Zeb1 have been correlated with poor patient outcomes in multiple cancers.
892-	ZEB2	↑	Zinc Finger E-Box Binding Homeobox 2			SIP1 (Smad Interacting Protein 1, also known as ZEB2) ZEB2 (Zinc Finger E-Box Binding Homeobox 2) is a transcription factor that plays a crucial role in the regulation of gene expression, particularly in the context of epithelial-to-mesenchymal transition (EMT) and cancer progression. ZEB2 has been found to be overexpressed in various types of cancer, including breast, lung, colon, and prostate cancer.
1320-	ZFX	↑	Zinc Finger X-linked			ZFX (Zinc Finger X-linked) is a transcription factor that plays an important role in regulating stem cell self-renewal, proliferation, and differentiation. -Several studies have demonstrated that ZFX is overexpressed in various malignancies, including hematological cancers and solid tumors. Elevated ZFX levels have been associated with enhanced self-renewal capacity, increased tumorigenicity, and resistance to apoptosis.
674-	ZO-1	↓	Zonula occludens-1			ZO-1 (Zonula occludens-1) is a protein that plays a crucial role in the formation and maintenance of tight junctions in epithelial cells. Tight junctions are essential for maintaining the integrity of epithelial barriers and regulating the passage of ions and molecules across the cell membrane. In the context of cancer, ZO-1 has been implicated in several ways: 1.Loss of ZO-1 expression: Reduced or lost expression observed in various types of cancer 2.Disruption of tight junctions: Cancer cells often exhibit disrupted tight junctions, which can lead to increased permeability and the loss of epithelial barrier function. ZO-1 is a key component of tight junctions, and its disruption can contribute to the development and progression of cancer. 3.Epithelial-to-mesenchymal transition (EMT): ZO-1 has been shown to play a role in regulating EMT, a process by which epithelial cells acquire a mesenchymal phenotype. EMT is a key event in the development of cancer metastasis, and ZO-1's role in regulating this process is an area of active research. 4.Tumor suppressor function: ZO-1 has been proposed to have tumor suppressor functions, and its loss or downregulation can contribute to the development of cancer. ZO-1's tumor suppressor functions may be related to its ability to regulate cell growth, apoptosis, and cell migration. ZO-1 generally acts as a tumor suppressor by maintaining epithelial integrity. In many cancers, downregulation or mislocalization of ZO-1 is observed and is associated with a poorer prognosis due to the facilitation of EMT and metastasis.
719-	α-SMA	↑	α-smooth muscle actin		protein	α-smooth muscle actin (α-SMA) is a protein that is often associated with cancer progression. It is a key component of the actin cytoskeleton and plays a crucial role in cell migration, invasion, and contraction. α-SMA is often expressed by cancer-associated fibroblasts (CAFs), which are a type of stromal cell that surrounds the tumor. CAFs expressing α-SMA can promote tumor growth and metastasis. High levels of α-SMA expression have been correlated with poor prognosis in various types of cancer, including breast, lung, and colorectal cancer.
933-	α-tubulin	↑	α-tubulin			α-Tubulin is a protein that is a component of microtubules, which are dynamic structures that play a crucial role in various cellular processes, including cell division, cell migration, and intracellular transport. High α-tubulin expression is associated with poor prognosis, increased tumor size, and metastasis. α-Tubulin expression is also correlated with resistance to chemotherapy and hormone therapy. Generally, high α-tubulin expression is associated with: Poor prognosis Increased tumor size Metastasis Resistance to chemotherapy and radiation therapy Poor response to treatment Low α-tubulin expression is associated with: Better prognosis Smaller tumor size Less metastasis Better response to chemotherapy and radiation therapy Better response to treatment
571-	β-Amyloid	↑	β-Amyloid Fibrils			Amyloid-β (Aβ) fibrils are the main component of amyloid plaques that develop in brain tissue of Alzheimer's disease (AD) patients.
342-	β-catenin/ZEB1	↑	β-catenin/ZEB1	HalifaxProj (inactivate)		β-catenin and ZEB1 are two important proteins that play significant roles in cancer biology, particularly in the processes of cell adhesion, epithelial-mesenchymal transition (EMT), and tumor progression. β-catenin is a key component of the Wnt signaling pathway, which is crucial for cell proliferation, differentiation, and survival. It also plays a role in cell-cell adhesion by linking cadherins to the actin cytoskeleton. Role in Cancer: ZEB1 is often upregulated in cancer and is associated with increased invasiveness and metastasis. It can repress epithelial markers (like E-cadherin) and promote mesenchymal markers (like N-cadherin and vimentin), facilitating the transition to a more aggressive cancer phenotype. (MMP)-2 and MMP-9, which are the down-stream targets of β-catenin and play a crucial role in cancer cell metastasis.
1276-	β-Endo	↓	β-Endorphin			β-Endorphin is an endogenous opioid peptide produced through the cleavage of proopiomelanocortin (POMC) primarily in the anterior pituitary. – It is well known for its roles in pain relief, stress reduction, and modulation of the immune system. – β-Endorphin can interact with opioid receptors expressed in various tissues, including cells within the tumor microenvironment. – Some studies indicate that increased β-endorphin or POMC expression might correlate with altered stress responses in cancer patients, which could indirectly influence survival outcomes. - In specific contexts, higher β-endorphin levels might be associated with improved pain control and quality of life, which could reflect in better overall outcomes.
1145-	β-oxidation	?	Beta Oxidation			Beta-oxidation serves as a major pathway for breaking down fatty acids into acetyl-CoA, which then enters the tricarboxylic acid (TCA) cycle to generate ATP. – In tumors with limited glucose availability or under metabolic stress, enhanced fatty acid oxidation can serve as an alternative energy source, supporting cell survival and proliferation. – Beta-oxidation contributes to the removal of excess fatty acids and provides substrates for oxidative phosphorylation, thereby influencing the balance between energy production and biosynthetic needs. – Tumor environments are often hypoxic and nutrient-deprived. Enhanced beta-oxidation can allow cancer cells to adapt by optimizing energy yield from available substrates. – Upregulated beta-oxidation or reliance on fatty acid metabolism in certain tumors has been correlated with increased aggressiveness, metastasis, and a poor overall prognosis.
751-	β-TRCP	↑	beta-transducin repeat-containing protein			β-TRCP (beta-transducin repeat-containing protein) is a protein that plays a crucial role in the regulation of various cellular processes, including cell cycle progression, apoptosis, and DNA damage response. It is a component of the SCF (Skp1-Cullin-F-box) complex, a type of E3 ubiquitin ligase that targets specific proteins for degradation by the proteasome. Overexpression of β-TRCP has been associated with poor prognosis and increased tumor aggressiveness. Elevated expression in: breast, lung, colon, prostate, ovarian, pancreatic, GBM HCC, Esophageal, Stomach.
606-	β1-integrin	↑	β1-integrin			a transmembrane receptor that plays a crucial role in cell adhesion, migration, and signaling. β1-integrin is overexpressed in various types of cancer, including breast, lung, colon, and melanoma.
667-	γH2AX	↑	gamma-H2AX			γH2AX (gamma-H2AX) is a histone protein that plays a crucial role in the repair of DNA double-strand breaks (DSBs). It is a phosphorylated form of the H2AX protein, which is a component of chromatin. γH2AX is often used as a biomarker for DNA damage and genomic instability. When DNA is damaged, the H2AX protein is phosphorylated, forming γH2AX, which recruits and activates DNA repair proteins to the site of damage. γ-H2AX, a marker for DNA double-strand breaks. Cancer cells often exhibit increased levels of γH2AX due to their high rate of DNA replication and repair errors. Gamma-H2AX, on the other hand, refers to a phosphorylated form of H2AX.
343-	γδ T-cell activity	↓	γδ T-cell activity	HalifaxProj (promote)		γδ T-cells are a unique subset of T-cells that play a significant role in the immune response, particularly in the context of cancer. Unlike conventional αβ T-cells, γδ T-cells possess distinct T-cell receptors (TCRs) composed of gamma and delta chains. This unique structure allows them to recognize a wide range of antigens, including those derived from stressed, infected, or transformed cells, making them particularly interesting in cancer immunology. – In many studies, higher levels or functional anti-tumor γδ T-cell activity (especially IFN-γ producing γδ T cells) have been associated with improved patient outcomes. – Their capability to recognize and directly kill stressed or transformed cells contributes to tumor immune surveillance. – γδ T cells can produce pro-inflammatory cytokines (like IFN-γ) that support anti-tumor immune responses. – Alternatively, in certain microenvironments, they may secrete IL-17 or other factors that could promote tumor-associated inflammation and even angiogenesis

 Home