PCA3

Prostate cancer antigen 3 (PCA3, also referred to as DD3) is a gene which has noncoding messenger RNA that is overexpressed in prostate cancer. This messenger RNA is useful as a tumor marker.

Use as biomarker

The most frequently used biomarker for prostate cancer today is the serum level of prostate-specific antigen (PSA), or derived measurements. However, since PSA is prostate-specific but not cancer-specific, it is an imperfect biomarker. For example, PSA can increase in older men with benign prostatic hyperplasia. Several new biomarkers are being investigated to improve the diagnosis of prostate cancer. Some of these can be measured in urine samples, and it is possible that a combination of several urinary biomarkers will replace PSA in the future.

Compared to serum PSA, PCA3 has a lower sensitivity but a higher specificity and a better positive and negative predictive value. It is independent of prostate volume, whereas PSA is not. It should be measured in the first portion of urine after prostate massage with digital rectal examination.

PCA3 has been shown to be useful to predict the presence of malignancy in men undergoing repeat prostate biopsy. This means that it could be useful clinicaly for a patient for whom digital rectal examination and PSA suggest possible prostate cancer, but the first prostate biopsy returns a normal result. This occurs in approximately 60% of cases, and on repeat testing, 20-40% have an abnormal biopsy result.

Other uses that are being studied for PCA3 include its correlation with adverse tumor features such as tumor volume, grading (Gleason score) or extracapsular extension. These studies have so far produced conflicting results.

A commercial kit called the Progensa PCA3 test is marketed by the Californian company Gen-probe. PCA3 Rights acquired from Diagnocure back in 2003. Royalties of 16% of cumulative sales of PCA3 kit are paid to Diagnocure. Diagnocure is quoted on TSX as CUR.TO (Canada)

Discovery

PCA3 was discovered to be highly expressed by prostate cancer cells in 1999.

Further reading

• Clarke RA, Zhao Z, Guo AY; et al. (2009). "New genomic structure for prostate cancer specific gene PCA3 within BMCC1: implications for prostate cancer detection and progression". PLoS ONE. 4 (3): e4995. doi:10.1371/journal.pone.0004995. PMID 19319183. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link) CS1 maint: unflagged free DOI (link)
• Schilling D, Hennenlotter J, Munz M; et al. (2010). "Interpretation of the prostate cancer gene 3 in reference to the individual clinical background: implications for daily practice". Urol. Int. 85 (2): 159–65. doi:10.1159/000314078. PMID 20424427. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Day JR, Jost M, Reynolds MA; et al. (2011). "PCA3: from basic molecular science to the clinical lab". Cancer Lett. 301 (1): 1–6. doi:10.1016/j.canlet.2010.10.019. PMID 21093148. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Schalken JA, Hessels D, Verhaegh G (2003). "New targets for therapy in prostate cancer: differential display code 3 (DD3(PCA3)), a highly prostate cancer-specific gene". Urology. 62 (5 Suppl 1): 34–43. PMID 14607216.{{cite journal}}: CS1 maint: multiple names: authors list (link)
• Ankerst DP, Groskopf J, Day JR; et al. (2008). "Predicting prostate cancer risk through incorporation of prostate cancer gene 3". J. Urol. 180 (4): 1303–8, discussion 1308. doi:10.1016/j.juro.2008.06.038. PMID 18707724. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Roobol MJ, Schröder FH, van Leeuwen P; et al. (2010). "Performance of the prostate cancer antigen 3 (PCA3) gene and prostate-specific antigen in prescreened men: exploring the value of PCA3 for a first-line diagnostic test". Eur. Urol. 58 (4): 475–81. doi:10.1016/j.eururo.2010.06.039. PMID 20637539. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Sokoll LJ, Ellis W, Lange P; et al. (2008). "A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance, and diagnostic accuracy". Clin. Chim. Acta. 389 (1–2): 1–6. doi:10.1016/j.cca.2007.11.003. PMID 18061575. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Hessels D, Schalken JA (2009). "The use of PCA3 in the diagnosis of prostate cancer". Nat Rev Urol. 6 (5): 255–61. doi:10.1038/nrurol.2009.40. PMID 19424173.
• Salagierski M, Verhaegh GW, Jannink SA; et al. (2010). "Differential expression of PCA3 and its overlapping PRUNE2 transcript in prostate cancer". Prostate. 70 (1): 70–8. doi:10.1002/pros.21040. PMID 19760627. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Haese A, de la Taille A, van Poppel H; et al. (2008). "Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy". Eur. Urol. 54 (5): 1081–8. doi:10.1016/j.eururo.2008.06.071. PMID 18602209. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Gandini O, Luci L, Stigliano A; et al. "Is DD3 a new prostate-specific gene?". Anticancer Res. 23 (1A): 305–8. PMID 12680228. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Hessels D, van Gils MP, van Hooij O; et al. (2010). "Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer". Prostate. 70 (1): 10–6. doi:10.1002/pros.21032. PMID 19708043. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Klecka J, Holubec L, Pesta M; et al. (2010). "Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis". Anticancer Res. 30 (2): 665–70. PMID 20332487. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Thelen P, Burfeind P, Grzmil M; et al. (2004). "cDNA microarray analysis with amplified RNA after isolation of intact cellular RNA from neoplastic and non-neoplastic prostate tissue separated by laser microdissections". Int. J. Oncol. 24 (5): 1085–92. PMID 15067329. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Tao Z, Shen M, Zheng Y; et al. (2010). "PCA3 gene expression in prostate cancer tissue in a Chinese population: quantification by real-time FQ-RT-PCR based on exon 3 of PCA3". Exp. Mol. Pathol. 89 (1): 58–62. doi:10.1016/j.yexmp.2010.01.008. PMID 20114043. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Hessels D, Klein Gunnewiek JM, van Oort I; et al. (2003). "DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer". Eur. Urol. 44 (1): 8–15, discussion 15-6. PMID 12814669. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)
• Mearini E, Antognelli C, Del Buono C; et al. (2009). "The combination of urine DD3(PCA3) mRNA and PSA mRNA as molecular markers of prostate cancer". Biomarkers. 14 (4): 235–43. doi:10.1080/13547500902807306. PMID 19489685. {{cite journal}}: Explicit use of et al. in: |author= (help)CS1 maint: multiple names: authors list (link)

External links

• prostate+cancer+antigen+3,+human at the U.S. National Library of Medicine Medical Subject Headings (MeSH)