Prostate Cancer Biomarkers

Candidate prostate cancer biomarker
Protein Names Clinical Markers Human Swiss Prot # Comments Quality Products
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
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
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
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
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 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 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 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
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 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
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
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
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
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
Acid phosphatase prostate   P15309 An enzyme produced by the prostate, it is increased in men with prostate cancer (Afzal et al. 2003).  
Alkaline phosphatase bone-specific   P05186 Bone specific alkaline phosphatase may play a role in skeletal mineralization. Bone-specific alkaline phosphatase was significantly increased in prostate cancer patients with bone metastases compared to patients without metastases (Jung et al. 2004).  
Apolipoprotein A-II   P02652 Associates with, stabilizes and regulates metabolism of HDL. ApoA-II is overexpressed both in tissues and serum from individuals with prostate cancer. ApoA-II was also overexpressed in the serum of individuals with prostate cancer who have normal prostate-specific antigen (0–4.0 ng/mL) (Malik et al. 2005).  
Bone sialoprotein II   P21815 A noncollagenous bone protein increased in prostate, colon, and breast cancer (Fedarko et al. 2001).  
Collagen I c-terminal telopeptide   P02452 Collagen is a structural protein, the c-terminal telopeptide is increased in patients with prostate cancer and bone metastasis (Garnero et al. 2000).  
Netrin-1   O95631 Signals axon growth and guidance. A reduction of NTN1 expression was observed in prostate tumors (Latil et al. 2003).  
Progesterone receptor yes P06401 The progesterone receptor is a steroid receptor which stimulates hormone-specific transcription of specific genes. There is a loss of expression in prostate cancer tissue (Ji et al. 2005).  
PSP94 binding protein   x It may be involved in hormonal control. It is lower in the serum of prostate cancer patients (Reeves et al. 2005).  
Prostate cancer biomarker background

Levels of prostate specific antigen in the blood can be increased by conditions besides prostate cancer. However, because high levels of prostate specific antigen cannot distinguish men who have prostate cancer from those whose levels are increased for another reason, most men with high levels are likely to undergo cancer tests. These tests include a digital rectal exam, possibly followed by a biopsy. As a result, many men will undergo a biopsy for prostate cancer that they actually do not have. This can be alarming for patients and their families, and can also increase healthcare costs. When screening large numbers of men for prostate cancer, we would prefer to have a test that is better at separating those who have cancer from those who do not.

On the other hand, levels of prostate specific antigen in the blood can be very useful in monitoring prostate cancer once it has been diagnosed. For instance reduced levels of this protein in the blood are a biomarker for effective treatment of prostate cancer. As explained by several investigators at the National Cancer Institute, "The arguments about use of PSA [prostate specific antigen] for screening continue, but its value in monitoring diagnosed prostate cancer or its treatment would be hard to dispute." (Ludwig, Weinstein, 2005)

The development of biomarkers for prostate cancer screening, detection, and prognostication has revolutionized the management of this disease. Prostate-specific antigen (PSA) is a useful, though not specific, biomarker for detecting prostate cancer. Prostate cancer biomarkers which have been studied on literatures includes serum markers (PAP, tPSA, fPSA, proPSA, PSAD, PSAV, PSADT, EPCA, and EPCA-2), tissue markers (AMACR, methylated GSTP1, and the TMPRSS2-ETS gene rearrangement), and a urine marker (DD3PCA3/UPM-3). Future research should focus on validation of already existing prostate cancer biomarkers and the discovery of new biomarkers to identify men with aggressive prostate cancer.

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