Table 1.
Summary of PCa biomarkers in the literature.
| Gene | Description | Gene type | Expression | Type of biomarker | Sample | References |
|---|---|---|---|---|---|---|
| AMACR (P504) | Alpha-Methylacyl-CoA Racemase | Enzyme involved in branched chain fatty acid oxidation | Over-expressed in PCa (also in HGPIN) and in some other carcinomas, both at RNA and protein level | Diagnostic (in gray zone) and prognostic | Tissue, blood and urine | [20,21] |
| ANXA3 | Annexin A3 | Calcium and phospholipid binding protein | Presence in urinary exosomes and proteasomes. Lower production in PCa than in BPH, HGPIN and benign | Prognostic (able to stratify a large group of intermediate-risk patients into high- and low-risk subgroups) | Tissue and urine | [22–24] |
| APC | Adenomatous polyposis coli | Tumor suppressor. Promotes rapid degradation of CTNNB1 and participates in Wnt signaling as a negative regulator. | APC methylation higher in PCa than in BPH. Methylation level correlates positively with Gleason score | Diagnostic and prognostic | Tissue and Urine DNA | [25] |
| AR | Androgen receptor | Receptor for androgen stimulation of prostate. | Over-expression associated with poor prognosis prostate cancer and metastasis | Prognostic | Tissue RNA and IHC | [26–28] |
| AURKA | Aurora kinase. | Aurora kinase. AURKA is a centrosome-associated serine/threonine kinase involved in mitotic chromosomal segregation. | Amplified and over-expressed in certain types of poor prognosis prostate cancer | Prognostic | Tissue RNA and DNA | [29–31] |
| AZGP1 | Alpha-2-glycoprotein 1, zinc binding. Alias. ZAG | Stimulates lipid degradation in adipocytes and causes the extensive fat losses associated with some advanced cancers. May bind polyunsaturated fatty acids. | Over-expressed in PCa. Low AZGP1 expression predicts for recurrence in margin-positive, localized PCa | Diagnostic, prognostic | Tissue, blood and urine | [32–34] |
| BRAF | v-raf murine sarcoma viral oncogene homolog B1 | Belongs to the raf/mil family of serine/threonine protein kinases and is involved in the regulation of the MAP kinase/ERKs signaling pathway, which affects cell division, differentiation. | SLC45A3-BRAF fusion gene, mutations and gain in prostate cancer | Diagnostic and therapeutic target | Tissue RNA and DNA | [35–37] |
| CAMKK2 | Calcium/calmodulindependent protein kinase kinase 2. | AR target gene promoting biosynthesis and glycolysis | Down-regulation of calcium/calmodulin-dependent protein kinase kinase 2 by androgen deprivation induces castration-resistant prostate cancer. | Prognostic | Tissue RNA | [38–40] |
| CDH1 | Cadherin 1, type 1, E-cadherin (epithelial) | Epithelial cell - cell adhesion molecule | Reduced production in 50% of tumors. E-cadherin production by epithelial cells has been shown to predict PCa prognosis | Prognostic (correlated with grade, tumor stage, and survival) | Tissue | [41,42] |
| CLU | Clusterin | Function unknown, but is thought to be involved in several basic biological events such as cell death and tumor progression. | Developed as a potential therapeutic target | Therapeutic target | Tissue, exosome protein | [43–46] |
| CRISP-3 | Cysteine-Rich Secretory Protein 3 | Secreted protein produced in the male reproductive tract, is involved in sperm maturation | Large amounts have been detected in seminal plasma. Over-expressed in HGPIN and PCa. | Prognostic | Tissue | [47,48] |
| EPCA | Early Prostate Cancer Antigen | Nuclear matrix protein | Over-expressed in PCa | Diagnostic (for predicting repeated BP) | Tissue and blood | [49,50] |
| EPCA-2 | Early Prostate Cancer Antigen 2 | Nuclear matrix protein | Over-expressed in PCa | Diagnostic and Prognostic (differentiate localized PCa from metastatic PCa) | Blood | [51] |
| FOLH1/PS MA | Folate hydrolase 1/Prostate Specific Membrane Antigen | Type II membrane protein. 1/N-acetylated-alpha-linked acidic dipeptidase | Over-expressed in PCa compared to BPH and normal | Diagnostic. Imaging marker and target for therapy | Tissue, blood and urine | [52,53] |
| GOLM1 | Golgi membrane protein 1 (GOLPH2) | Cis-Golgi membrane protein of unknown function | Over-expressed in PCa | Diagnostic | Urine | [54,55] |
| GSTP1 | Glutathione S-transferase P1 | Enzyme involved in protecting DNA from free radicals | Loss of GSTP1 expression due to the promoter hypermethylation (>90% of PCa). Correlates with the number of cores found to contain PCa | Diagnostic (indicator for repeat biopsy) | Tissue and urine DNA | [56,57] |
| HPN | Hepsin | Membrane serine protease | Over-expressed in 90% PCa tumors (highly produced in HGPIN and PCa compared with BPH) | Diagnostic | Tissue | [58,59] |
| IL-6 | Interleukin-6 | Cytokine secreted by a variety of cell types, is involved in the immune and acute-phase response | Increased concentrations of IL-6 and IL-6R in metastatic and androgen-independent PCa | Diagnosis and Prognostic | Blood | [60–62] |
| IMPDH2 | IMP (inosine 5′-monophosphate) dehydrogenase 2 | Myc target gene associated with nucleotide biosynthesis | Increased serum level associated with the clinicopathological features of the patients with PCa | Diagnostic | Blood | [63] |
| KLK2 | Human Kallikrein 2 | Secreted serine protease | Over-expressed during PCa progression | Diagnostic and Prognostic | Tissue and blood | [64,65] |
| KLK3 (PSA) | Kallikrein-related peptidase 3 (Prostate-Specific Antigen) | Secreted serine protease. Serum level of this protein, called PSA in the clinical setting, is useful in the diagnosis and monitoring of PCa. | Increased expression associated with malignant PCa | Diagnostic | Blood, urine | [66] |
| KLK4 | Kallikrein-related peptidase 4 | One of fifteen kallikrein subfamily members located in a cluster on chromosome 19 | Increased expression associated with malignant PCa | Prognostic | Tissue RNA and IHC | [67,68]. |
| MAP3K5 | Mitogen-activated protein kinase kinase kinase 5 | Signaling cascade | Increased expression associated with PCa | Prognostic | Tissue RNA and IHC | [69] |
| MKI67 | Encoding antigen identified by monoclonal antibody Ki-67 | Tumor growth marker, encodes a nuclear protein that is associated with and may be necessary for cellular proliferation | Increased expression associated with malignant prostate cancer | Prognostic | Tissue | [70–72] |
| MMP26 | Matrix metallo peptidase 26 | Involved in the breakdown of extracellular matrix in normal physiological processes and cancer metastasis. | Highest expression in HGPIN and decline in cancer, possible involvement in formation of early cancer. | Progression | Tissue RNA | [73–76] |
| MMP9 | Matrix metallo proteinase 9 | Implicated in invasion and metastasis of human malignancies | Over-expressed in PCa | Diagnostic | Urine | [77,78] |
| OR51E2/PS GR | Prostate Specific G-coupled Receptor | Receptors coupled to heterotrimeric GTP-binding proteins | Over-expressed in PCa | Diagnostic | Tissue and urine | [79–81] |
| PAP | Human Prostatic acid phosphatase | Enzyme | Over-expressed in PCa and in bone metastasis | Diagnostic and Prognostic of PCa bone metastasis | Blood and urine | [82,83] |
| PCA3 | Prostate Cancer Gene 3 | Non coding mRNA | Prostate specific and highly up-regulated in PCa | Diagnostic (indicator for repeat biopsy) | Tissue and urine | [84–93] |
| PDIA3 | Protein disulfide isomerase family A, member 3. | Endoplasmic reticulum that interacts with lectin chaperones calreticulin and calnexin to modulate folding of newly synthesized glycoproteins. | Increased expression associated with malignant PCa | Prognostic | Tissue RNA and IHC | [69] |
| PSCA | Prostate Stem Cell Antigen | Membrane glycoprotein | Specific production in the prostate and possible target for therapy | Prognostic (correlated with higher Gleason score, higher stage, and the presence of metastasis) | Tissue and blood | [94,95] |
| RARB | Retinoic acid receptor, beta | Binds retinoic acid. Mediates signalling in embryonic morphogenesis, cell growth and differentiation. | DNA methylation | Prognostic | Tissue and urine DNA | [96,97] |
| RASSF1A | Ras association (RalGDS/AF-6) domain family member 1 | Potential tumor suppressor. Required for death receptor-dependent apoptosis | DNA methylation | Prognostic | Tissue and urine DNA | [97] |
| Sarcosine | Sarcosine | N-methyl derivative of the amino-acid glycine | Seems to be differentially expressed metabolite elevated during PCa progression to metastasis | Prognostic | Urine and blood | [98] |
| SPINK1 | Serine peptidase inhibitor, Kazal type 1 | Serine peptidase inhibitor | Overexressed in a portion of non-ETS translocated tumors | Diagnostic | Urine, tissue | [54,99] |
| TERT | Telomerase reverse transcriptase | Maintains the telomeric ends of chromosomes and if telomerase is active, cancer cells may escape cell cycle arrest and replicative senscence | Amplification in PCa, significative association with Gleason score | Prognostic | Urine and blood | [57,100,101] |
| TGFB1 | Transforming growth factor-b1 | Growth factor involved in cellular differentiation, immune response, angiogenesis, and proliferation | Role of TGFβ1 in PCa progression. | Prognostic (Correlation with tumor grade and stage and lymph node metastasis) | Tissue and blood | [62,102,103] |
| TIMP4 | TIMP metallopeptidase inhibitor 4 | Inhibitors of the matrix metallo proteinases | Highest expression in HGPIN and decline in cancer, possible involvement in formation of early cancer. | Progression | Tissue RNA | [73–75] |
| TMPRSS2:E RG | 5′ UTR of the prostate-specific androgen regulated transmembrane protease serine2 and v-ETS erythroblostosis virus E26 oncogene homolog | Gene fusion; androgen drives the expression of ETS-TF and causes tumor proliferation | The most common gene fusion in PCa. Over-expressed PCa and related to PCa aggressiveness | Prognostic for aggressive PCa and detection of PCa | Tissue and urine | [104–106] |
| PLAU and UPAR | Plasminogen Activator, Urokinase and Receptor | Degradation of extra cellular matrix | Over-expressed in BPH and PCa vs benign | Prognostic (increased uPA and uPAR in PCa patients with bone metastasis) | Tissue and blood | [107,108] |