Candidate Cancer Biomarker

The candidate cancer biomarkers include proteins involved in oncogenesis, angiogenesis, development, differentiation, proliferation, apoptosis, hematopoiesis, immune and hormonal responses, cell signaling, nucleotide function, hydrolysis, cellular homing, cell cycle and structure, the acute phase response and hormonal control.

Given the size of the list of candidate cancer biomarkers, researchers have selected a smaller subset of higher priority candidates as a starting point for consideration of assay development and clinical validation. Various high-priority candidate cancer biomarkers will be listed according to different hot cancers. For example, candidate breast cancer biomarkers, candidate lung cancer biomarkers, candidate prostate cancer biomarkers, candidate ovarian cancer biomarkers, candidate pancreatic cancer biomarkers, candidate colon cancer biomarkers, and so on.

Candidate cancer biomarkers
Protein Names Clinical Markers Human Swiss Prot # Comments Quality Products (Protein, antibody, ELISA kit & cDNA clone)
Adrenomedullin yes P35318 Adrenomedullin is a hypotensive peptide increased in gastrointestinal tract and lung cancer (Ehlenz et al. 1997). Adrenomedullin / ADM
Alpha-2-macroglobulin   P01023 A serum plasma proteinase inhibitor with a wide specificity, it is decreased in prostate cancer with metastases (Kanoh et al. 2001). alpha-2-macroglobulin
Angiopoietin 1   Q15389 Involved in vasculature modeling, it is increased in breast cancer (Caine et al. 2003). Angiopoietin 1 / ANG1 / ANGPT1
Angiopoietin 2   O15123 It is involved in vasculature modeling in that it is an antagonist of angiopoietin 2. It is increased in breast cancer (Caine et al. 2003). Angiopoietin-2 / ANG2
DNA-(apurinic or apyrimidinic site) lyase, APEX   P27695 A DNA repair enzyme, increased immuno histochemical staining seen in prostate cancer tissue (Kelley et al. 2001). APEX1/AP/APEx/Ref-1
Apolipoprotein A1   P02647 Apolipoprotein A-I is the major apoprotein of HDL. ApoA-I also promotes efflux of cholesterol from cell. It is decreased ovarian cancer (Zhang et al. 2004). ApoA1
B-cell CLL/lymphoma 2   P10415 An inhibitor of apoptosis Bcl-2 maintains homeostasis in the immune system The differing effects of Bcl-2 expression on prognosis may be due to which cells are expressing the Bcl-2, immune cells or tumors. High expression in ovarian cancer (Herod et al. 1996) and non small lung cancer (Shibata et al. 2004) are associated with better prognosis whereas well differentiated tumors more likely to be Bcl-2 positive (Soda et al. 1999). BCL2 / Bcl-2
Brain-derived neurotrophic factor   P23560 It promotes the survival of neuronal populations and is differentially expressed in ovarian cancer (Mor et al. 2005). BDNF
Breast cancer 2 early onset   P51587 BRCA2 is a breast cancer susceptibility gene. Five percent of early onset breast cancer cases express mutations in Brca 1 or 2 (Lalloo and Evans 1999). BRCA2
Cathepsin B   P07858 A major cysteine protease involved in antigen degradation, it is overexpressed in tumors of the lung, prostate, colon, breast, stomach and esopha- geal adenocarcinoma (Hughes et al. 1998). Cathepsin B
CC chemokine 4, HCC-4   O15467 A chemotactic and myelosuppressive factor, differentially expressed in ovarian cancer (Mor et al. 2005). CCL16/HCC-4
Small inducible cytokine A2(CCL2)   P13500 CCL2 is a monocyte, chemotactic and activating factor increased in some breast cancer (Lebrecht et al. 2004). CCL2/MCP-1
Small inducible cytokine A21 (CCL21)   O00585 CCL21 inhibits hematopoiesis and stimulates chemotaxis. It is differentially expressed in ovarian cancer (Mor et al. 2005). CCL21/6Ckine
Platelet endothelial cell adhesion molecule, PECAM-1   P16284 Involved in transendothelial migration of leukocytes, angiogenesis, and integrin activation; it is underexpressed in adenocarinomas of the lung (McDoniels-Silvers et al. 2002) but decreased in patients with recurrent basal cell carcinoma (Yerebakan et al. 2003). CD31/PECAM-1
Tumor necrosis factor (ligand) superfamily member 5, CD154   P29965 CD154 is a B cell stimulator increased in lung cancer (Roselli et al. 2004). CD40L/CD154/TNFSF5
CD44 antigen   P16070 Certain CD44 isoforms that regulate activation and migration of lymphocytes and macrophages may also enhance local growth and metastatic spread of tumor cells. Present in serum of normal individuals it is elevated in the serum from gastric and colon cancer patients, (Guo et al. 1994), Hodgkin's lymphoma patients(Lockhart et al. 1999), and acute leukemia patients (Yokota et al. 1999). CD44
Chitinase-3 like protein 1, YKL-40   P36222 YKL-40 (cartilage gp-39), is a mammalian glycoprotein related in sequence to chitinases. Its function is unknown, but it is thought to be involved in tissue remodeling (De Ceuninck et al. 2001). YKL-40 may represent a novel marker for the detection of early-stage ovarian cancer (Dupont et al. 2004). CHI3L1/YKL40
Coagulation factor XIII B chain   P05160 The protein carrier subunit of factor XIII, it crosslinks fibrin. It is decreased in breast cancer tissues (Jiang et al. 2003). Coagulation Factor XIII B chain
Complement component 7   P10643 An effector of innate and adaptive immunity, its mRNA is decreased in oesophageal, colon and kidney cancers (Oka et al. 2001). Complement component 7
C-reactive protein   P02741 An inflammation indicator, increased CRP levels are considered to be an important risk factor for atherosclerosis, myocardial infarction, peripheral vascular disease, and ischemic stroke. It is positively correlated with weight loss, anorexia-cachexia syndrome, extent of disease, and recurrence in advanced cancer. Its role as a predictor of survival has been shown in multiple myeloma, melanoma, lymphoma, ovarian, renal, pancreatic, and gastrointestinal tumors (Mahmoud and Rivera 2002). CRP/C-Reactive Protein
Cystatin C   P01034 The most abundant extracellular inhibitor of cysteine proteases, it is produced in all organs. It is decreased in squamous cell carcinoma of the head and neck (Strojan et al. 2004a) and in serum from ovarian cancer patients however, protein expression in ovarian cancer tissue is increased (Nishikawa et al. 2004). Cystatin C/CST3
Neutrophil defensin 1   P59665 An antimicrobial protein secreted by neutrophils increased in colon cancer patients (Albrethsen et al. 2005). Concentration given is for all three defensins together 1,2 & 3. DEFA1
Endothelin 1 yes P05305 Endothelin is a vasoconstrictor significantly elevated in 80% of primary human colon cancers (Kim et al. 2004). EDN1
Epidermal growth factor   P01133 Epidermal growth factor stimulates the growth of various epidermal and epithelial tissues, it is differentially expressed in ovarian cancer (Mor et al. 2005). EGF
Endoglin   P17813 An angiogenesis factor increased in breast cancer (Li et al. 2000). Endoglin/CD105
Erythropoietin   P01588 A stimulator of erythropoiesis associated with malignant cells and tumor vasculature in breast cancer (Acs et al. 2001). Erythropoietin / EPO
E-selectin   P16581 An adhesion molecule, sE-selectins increased in metastatic breast cancer especially in patients with liver metastases (Hebbar and Peyrat 2000). E-Selectin/CD62e/SELE
Follistatin   P19883 An activin antagonist, follistatin inhibits the biosynthesis and secretion of pituitary follicle stimulating hormone. It is differentially expressed in ovarian cancer (Mor et al. 2005). Follistatin
Growth arrest and DNA-damage- inducible alpha   P24522 GADD45A is strongly induced by ultraviolet radiation and alkylating agents and may be an effector of processes that regulate prostate cancer cell survival (Shain 2004). GADD45A
Interleukin 6 signal transducer   P40189 A signal transducer molecule, increased in breast cancer (Karczewska et al. 2000). gp130/CD130
Hepatocyte growth factor yes P14210 A growth factor for a broad spectrum of tissues and cell types. Hepatocyte growth factor has no detectable protease activity. It is increased in breast cancer tissues (Parr et al. 2004). HGF / Hepatocyte Growth Factor
Intercellular Adhesion Molecule 1   P05362 A lymphocyte adhesion molecule elevated in melanoma (Boyano et al. 2000), hepatocellular cancer (Tsujisaki et al. 1991), breast cancer (Altomonte et al. 1999), and extranodal lymphomas (Lei and Johnson 2000). ICAM-1/CD54
Interferon-alpha/beta receptor alpha chain   P17181 IFN receptor activation inhibits viral replication. In increasing order, higher levels are seen in benign hypertrophy, urolithiasis, bladder cancer , renal cell carcinoma, and prostate cancer (Kanayama et al. 2000). Concentrations for the complexed receptor. IFNAR1
Interferon-alpha/beta receptor beta chain   P48551 IFN receptor activation inhibits viral replication. In increasing order, higher levels are seen in benign hypertrophy, urolithiasis, bladder cancer, renal cell carcinoma, and prostate cancer (Kanayama et al. 2000). Concentrations for the complexed receptor. IFNAR2
Prostate secretory protein PSP94   P08118 Inhibits follicle-stimulating-hormone secretion, PSP94 serum measurements, especially of bound and free forms, have potential clinical utility in prostate cancer management (Reeves et al. 2005). IGBF/PRSP
Insulin-like growth factor 1 (somatomedin C)   P01343 Insulin-like growth factor 1 plays an important role in growth and development. It is decreased in endometrial cancer (Oh et al. 2004) and Non-Hodgkins' Lymphoma (Mohnike et al. 1995) but increased in prostate cancer (Stattin et al. 2000). IGF-1/IGF-I/IGF1
Insulin-like growth factor binding protein 1   P24591 Insulin-like growth factor binding proteins carry insulin-like growth factor thereby regulating its activity. It is differentially expressed in ovarian cancer (Mor et al. 2005). IGFBP1/IGFBP-1 
Insulin-like growth factor binding protein 3   P17936 Insulin-like growth factor binding proteins carry insulin-like growth factor thereby regulating its activity. It is decreased in endometrial cancer (Oh et al. 2004) and Non-Hodgkins' Lymphoma (Mohnike et al. 1995) but increased in prostate cancer (Stattin et al. 2000). IGFBP3
Interleukin 1 alpha   P01583 An inflammation and innate immunity modulator, IL-1 alpha is increased in ovarian cancer (Kondera-Anasz et al. 2003). IL-1 alpha / IL-1F1 / IL1A
Interleukin 1 beta   P01584 IL-1 beta is an inflammation and innate immunity modulator, loss of activity seen in prostate cancer (Ricote et al. 2004). IL-1 beta
Interleukin 2 yes P60568 A T cell growth factor with roles in the specific immune system, expression of IL-2 is high in infiltrative breast tumors (Garcia-Tunnon et al. 2004). IL-2
Interleukin 6   P05231 IL-6 is a cytokine that activates both innate and specific immune pathways. It is present in patients with metastatic renal (Walther et al. 1998), prostate (Adler et al. 1999), oral cavity and oropharyngeal squamous cell carcinoma (St. John et al. 2004). IL-6
Interleukin 6 receptor   P08887 An inflammation marker receptor that regulates the immune response, acute-phase reactions and hematopoiesis, it is significantly elevated in multiple myeloma patients (Alexandrakis et al. 2003). IL6 receptor mRNA was detected in 53% of breast carcinoma tissues and is associated with earlier stages of the disease. In advanced stages, expression of IL-6 and its receptor subunits predicts better prognosis (Karczewska et al. 2000). IL-6R/CD126
Interleukin 7   P13232 Il-7 stimulates hematopoiesis, it is increased in ovarian cancer (Xie et al. 2004). IL7 / interleukin-7
Inhibin yes various A glycoprotein hormone which regulates pituitary FSH, it is increased in postmenopausal ovarian cancer patients (Khosravi et al. 2004). Inhibin alpha/INHA; Inhibin beta A/INHBA; Inhibin beta B/INHBB; Inhibin beta C/INHBC;  Inhibin beta E/INHBE; 
Insulin yes P01308 Serum insulin levels were clearly higher in patients with breast cancer than in patients with benign breast disease and healthy controls (Han et al. 2005). Insulin Receptor
Kallikrein 10 yes O43240 Kallikrein 10 suppresses breast and prostate cancer. It is increased in tissues and serum of patients with ovarian cancer (Yousef and Diamandis 2002). KLK10
Kallikrein 11 yes Q9UBX7 A serine protease that may be involved in tissue remodeling and cell migration, it is elevated in ovarian cancer (Yousef et al. 2003). KLK11/Kallikrein 11
Kallikrein 2 prostatic   P20151 A serine endopeptidase, kallikrein 2 may predict pathologically organ confined prostate cancer in patients with stage T2 disease but not in stageT1c (Haese et al. 2005). KLK2
Kallikrein 3 (prostate specific antigen) yes P07288 PSA hydrolyzes the high molecular mass seminal vesicle protein thus leading to the liquid fraction of the seminal coagulum It is increased in men with prostate cancer (Thakur et al. 2003). KLK3/Kallikrein 3
Kallikrein 6 yes Q92876 A serine protease that may be useful in the diagnosis and monitoring of ovarian and prostate cancer (Yousef and Diamandis 2002). Increased plasma levels are also present in Alzheimer's disease (Diamandis et al. 2000). KLK6/Kallikrein 6/Neurosin
Kallikrein 7 yes P49862 Kallikrein 7 is a peptidase increased in ovarian cancer tissues (Yousef et al. 2003). KLK7/Kallikrein 7(PRSS6)
Kallikrein 8 yes O60259 Kallikrein 8 is a peptidase increased in ovarian cancer tissues (Yousef et al. 2003). KLK8/Kallikrein 8
k-ras   P01116 An oncogene product found in approximately 90% of human pancreatic cancer (Sakuma et al. 2004). 22.5% of ovarian cancers expressed K-ras codon 12 point mutations (Semczuk et al. 2004). K-Ras
Keratin 18   P05783 Keratin 18 is one of the first intermediate filament proteins expressed in the embryo. A monoclonal antibody to epithelium-specific keratin 18 stained the majority of inner cells in benign breast lesions but comparatively fewer such cells in carcinoma in situ and invasive carcinoma (Rudland et al. 1993). KRT18
Lactotransferrin   P02788 An iron-binding protein that modulates iron metabolism, hematopoiesis, and immunologic reactions. It is increased in gastrointestinal, lung and breast cancer patients (Vasil'ev and Avdeev 1985). Lactotransferrin/LTF
Mac-2 Binding Protein 90K   Q08380 Promotes integrin-mediated cell adhesion, it is increased in breast (Iacobelli et al. 1994) and hepatocellular cancer (Iacovazzi et al. 2001). LGALS3BP
Colony stimulating factor 1 (macrophage) yes P09603 A modulator that increases production of inflammatory leukocytes from the bone marrow, it is increased in ovarian cancer (Skates et al. 2004). M-CSF/CSF-1
Midkine   P21741 Midkine has heparin binding activity, and growth promoting activity, it is increased in breast cancer patients (Ikematsu et al. 2000). Midkine
Nerve growth factor beta   P01138 Nerve growth factor is important for the development and maintenance of the sympathetic and sensory nervous systems. Immunostaining for nerve growth factor-beta in esophageal and breast carcinomas demonstrated its immunoreactivity in stromal fibroblasts and some TrkA-expressing tumor cells (Koizumi et al. 1998). NGF/NGFB
Gamma enolase   P09104 Neuron specific enolase, a glycolytic enzyme, is released into the CSF when neural tissue is injured. Neoplasms derived from neural or neuro-endocrine tissue may release NSE into the blood. Elevated levels are found in seminomas (Fossa et al. 1992), advanced non-small cell lung cancer (Barlesi et al. 2004), solid malignant tumors and malignant hematologic disorders (Burghuber et al. 1990). NSE / ENO2 / Enolase 2
Secreted phosphoprotein 1, osteopontin   P10451 An extracellular matrix protein of pleiotropic properties including inflammation modulator, it is increased in prostate, colon, breast and lung cancer (Fedarko et al. 2001). Osteopontin/SPP1/ETA-1
Cyclin-dependent kinase inhibitor 1, p21   P38936 P21 is a cyclin-dependent kinase inhibitor that blocks cell cycle progression. It is suppressed in malignant nasopharyngeal epithelial cells(Fung et al. 2000), but overexpressed in pancreatic ductal adenocarcinoma (Hermanova et al. 2004). p21/WAF1/CDKN1A
Cellular tumor antigen p53   P04637 The p53 tumor suppressor protein regulates proliferation, cell cycle checkpoints, and apoptosis. More than one half of all lung cancers contain a mutation of the p53 tumor suppressor gene (Johnson and Kelley 1993). p53/TP53
Proliferating cell nuclear antigen   P12004 A DNA repair protein. Increased levels in breast cancer (Kushlinskii et al. 2004). PCNA
Urokinase plasminogen activator surface receptor, U-PAR   Q03405 The urokinase-type plasminogen activator receptor is a key molecule in the regulation of cell-surface plasminogen activation. It is increased in colorectal cancer and associated with poor prognosis in patients with metatatic breast cancer (Begum et al. 2004). PLAUR/CD87
Serum paraoxonase/ arylesterase 1   P27169 Hydrolyzes the toxic metabolites of a variety of organophosphorus insecticides. It is decreased in gastric (Akcay et al. 2003b) and pancreatic (Akcay et al. 2003a) cancer patients. PON1
transthyretin   P02766 A thyroid hormone binding protein decreased in ovarian cancer patients (Zhang et al. 2004). Prealbumin/Transthyretin
Parathyroid Hormone   P01270 Stimulates bone formation A correlation between tumor activity and ACTH, CT and PTH levels was shown in 50.44 and 47% of lung cancer patients respectively (Ausekar et al. 1985). PTH / PTH1 / Parathyroid Hormone
Parathyroid hormone-related protein yes P12272 A critical regulator of cellular and organ growth, development, migration, differentiation and survival and of epithelial calcium ion transport; parathyroid hormone-related protein is found in the serum of bone metastases (Iguchi et al. 2004), lung cancer (Nishigaki et al. 1999) patients and a multiple myeloma patient (Kitazawa et al. 2002). PTHLH
Squamous cell carcinoma antigen 1   P29508 A member of the ovalbumin family of serine proteinase inhibitors, it serves as a serologic marker for advanced squamous cell carcinomas of the uterine cervix, lung, esophagus, head and neck and vulva. Recent molecular studies show that SCCA is transcribed by two nearly identical genes (SCCA1 and SCCA2) that encode for members of the high molecular weight serine proteinase inhibitor (serpin) family (Cataltepe et al. 2000). SERPINB3 / SCCA-1
Antileukoproteinase 1, SLPI   P03973 An acid-stable proteinase inhibitor with strong affinity for trypsin and chymotrypsin as well as for neutrophil lysosomal elastase and cathepsin G, it is elevated in ovarian cancer patients (Tsukishiro et al. 2005). SLPI
Pancreatic secretory trypsin inhibitor, TATI   P00995 It is secreted from pancreatic acinar cells into pancreatic juice. Its physiologic role has been thought to be the prevention of trypsin-catalyzed premature activation of zymogens within the pancreas and the pancreatic duct. Since it is also found in serum and in various normal and malignant tissues, it may have other roles as well. It is elevated in ovarian cancer (Medl et al. 1995). SPINK1
Tetranectin   P05452 A plasma protein that has a specific binding affinity for sulfated polysaccharides and the kringle 4 of plasminogen, it is an independent prognostic factor in ovarian cancer (Begum et al. 2004). Tetranectin/CLEC3B
Transforming growth factor alpha   P01135 TGF-alpha, a potent mitogenic polypeptide, is present in most gallbladder carcinoma tissue (Lee 1998) and the plasma of ovarian cancer patients (Chien et al. 1997). TGF-alpha
Transforming growth factor beta 1   P01137 A transforming growth factor, regulated at the protein level with both inhibitory and stimulatory activities. TGF-beta 1 levels are increased in patients with prostate lymph node and bone metastases (Shariat et al. 2001), invasive bladder cancer (Eder et al. 1996) and cervical cancer (Dickson et al. 2000). TGF-beta 1
TGF-beta receptor type III   Q03167 A TGF-beta binding protein, it may retain TGF-beta for the signaling receptors. It is differentially expressed in ovarian cancer (Mor et al. 2005). TGFBR3
TEK tyrosine kinase endothelial, Tie-2   Q02763 Tie-2 is involved in angiogenesis, vasculogenesis and hematopoiesis. Increased in breast and prostate cancer (Caine et al. 2003). Tie2CD202b/TEK
Tissue inhibitor of metalloproteinase 2   P16035 TIMPs can form complexes with extracellular matrix metalloproteinases (such as collagenases) and irreversibly inactivate them. TIMP-2 is reduced in prostate cancer (Lichtinghagen et al. 2003). TIMP-2/TIMP2
Tumor necrosis factor (TNF-alpha)   P01375 TNF-alpha is a proinflammatory protein detected in the serum of 36.5% of pancreatic cancer patients. Patients with metastatic disease showed significantly higher positive serum TNF-alpha compared to those with non-metastatic disease (Karayiannakis et al. 2001). TNF-alpha/TNFA
Plasminogen (Contains Angiostatin)   P00747 The precursor to angiostatin, a potent angiogenesis inhibitor, it is increased in patients with malignant neoplasm of stomach, colon, lung, bladder, breast. renal pelvis, and prostate but decreased in patients with malignant neoplasm of biliary tree, pancrease, cervix uteri, kidney except pelvis, and thyroid (Chang Kyou et al. 2004). tPA
Trypsin   P07477 A hydrolytic enzyme whose activity was significantly lower in hepatocellular cancer tissue (Niewczas et al. 2002) but not altered in pancreatic, stomach, colon, rectal, lung or breast adenocarcinomas. Trypsin 2 / PRSS2
Trypsin   P07477 A hydrolytic enzyme whose activity was significantly lower in hepatocellular cancer tissue (Niewczas et al. 2002) but not altered in pancreatic, stomach, colon, rectal, lung or breast adenocarcinomas. Trypsin 2/PRSS2
Vascular cell adhesion molecule 1   P19320 VCAM-1 mediates the adhesion of monocytes and lymphocytes to cytokine-activated endothelium. It is correlated with microvessel density in early breast cancer tumors and increased in women with lymph node-positive and high-grade breast tumors (Byrne and Bundred 2000). VCAM-1/CD106
Fms-related tyrosine kinase 1, VEGFR1   P17948 An oncogene that is important for the control of cell proliferation and differentiation, it is reduced in breast cancer (Caine et al. 2003). VEGFR1/FLT-1
Vascular endothelial growth factor receptor 2   P35968 The VEGF-flk-1 system takes part in tumor angiogenesis, proliferation, and apoptosis in colon liver metastases (Cheng et al. 2004). VEGFR2/Flk-1/CD309/KDR
X box binding protein-1   P17861 A transcription factor essential for hepatocyte growth, the differentiation of plasma cells, immunoglobulin secretion, and the unfolded protein response. It is increased in identical twins with multiple myeloma(Munshi et al. 2004) hXBP-1 mRNA expression was increased in primary breast cancers but hardly detectable in non-cancerous breast tissue (Fujimoto et al. 2003). XBP1
17beta- Hydroxysteroid dehydrogenase type 1 (17HSD1)   x 17HSD1 converts estrone to estradiol in the ovary, placenta and the breast. Signals for 17HSD1 mRNA were detected in 16% of breast cancer specimens (Oduwole et al. 2004).  
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