PCA3

Prostate cancer associated 3 (non-protein coding)
Identifiers
Symbols PCA3 ; DD3; NCRNA00019; PCAT3
External IDs OMIM: 604845 GeneCards: PCA3 Gene
Orthologs
Species Human Mouse
Entrez 50652 n/a
Ensembl ENSG00000225937 n/a
UniProt n/a n/a
RefSeq (mRNA) n/a n/a
RefSeq (protein) n/a n/a
Location (UCSC) Chr 9:
76.76 – 76.79 Mb		 n/a
PubMed search n/a

Prostate cancer antigen 3 (PCA3, also referred to as DD3) is a gene that expresses a non-coding RNA. PCA3 is only expressed in human prostate tissue, and the gene is highly overexpressed in prostate cancer.[1][2] Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.[3]

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.[4]

Compared to serum PSA, PCA3 has a lower sensitivity but a higher specificity and a better positive and negative predictive value.[5] It is independent of prostate volume, whereas PSA is not.[6] It should be measured in the first portion of urine after prostate massage with digital rectal examination.[7]

PCA3 has been shown to be useful to predict the presence of malignancy in men undergoing repeat prostate biopsy.[7][8] This means that it could be useful clinically 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.[9]

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.[10][11][12]

A commercial kit called the Progensa PCA3 test is marketed by the Californian company Gen-Probe. Gen-Probe acquired rights to the PCA3 test from Diagnocure in 2003. Royalties of 16% of cumulative sales of PCA3 kit are paid to Diagnocure. Diagnocure is quoted on TSX as CUR.TO (Canada) [9] [13]

Discovery

PCA3 was discovered to be highly expressed by prostate cancer cells in 1999.[1]

References

  1. 1 2 Bussemakers MJ, van Bokhoven A, Verhaegh GW, et al. (December 1999). "DD3: a new prostate-specific gene, highly overexpressed in prostate cancer". Cancer Res. 59 (23): 5975–9. PMID 10606244.
  2. ↑ Neves AF, Araújo TG, Biase WK, et al. (July 2008). "Combined analysis of multiple mRNA markers by RT-PCR assay for prostate cancer diagnosis". Clin. Biochem. 41 (14-15): 1191–8. doi:10.1016/j.clinbiochem.2008.06.013. PMID 18640109.
  3. ↑ Loeb S (July 2008). "Does PCA3 Help Identify Clinically Significant Prostate Cancer?". Eur. Urol. 54 (5): 980–1. doi:10.1016/j.eururo.2008.07.027. PMID 18684556.
  4. ↑ Laxman B, Morris DS, Yu J, et al. (February 2008). "A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer". Cancer Res. 68 (3): 645–9. doi:10.1158/0008-5472.CAN-07-3224. PMC 2998181. PMID 18245462.
  5. ↑ Vlaeminck-Guillem V, Ruffion A, Andre J (May 2008). "[Value of urinary PCA3 test for prostate cancer diagnosis]". Prog. Urol. (in French) 18 (5): 259–65. doi:10.1016/j.purol.2008.03.029. PMID 18538269.
  6. ↑ Deras IL, Aubin SM, Blase A, et al. (April 2008). "PCA3: a molecular urine assay for predicting prostate biopsy outcome". J. Urol. 179 (4): 1587–92. doi:10.1016/j.juro.2007.11.038. PMID 18295257.
  7. 1 2 Haese A, de la Taille A, van Poppel H, et al. (June 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.
  8. ↑ Marks LS, Fradet Y, Deras IL, et al. (March 2007). "PCA3 molecular urine assay for prostate cancer in men undergoing repeat biopsy". Urology 69 (3): 532–5. doi:10.1016/j.urology.2006.12.014. PMID 17382159.
  9. 1 2 de la Taille A (September 2007). "Progensa PCA3 test for prostate cancer detection". Expert Rev. Mol. Diagn. 7 (5): 491–7. doi:10.1586/14737159.7.5.491. PMID 17892357.
  10. ↑ Nakanishi H, Groskopf J, Fritsche HA, et al. (May 2008). "PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance". J. Urol. 179 (5): 1804–9; discussion 1809–10. doi:10.1016/j.juro.2008.01.013. PMID 18353398.
  11. ↑ van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, et al. (August 2008). "Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results". Prostate 68 (11): 1215–22. doi:10.1002/pros.20781. PMID 18500693.
  12. ↑ Whitman EJ, Groskopf J, Ali A, et al. (September 2008). "PCA3 Score Before Radical Prostatectomy Predicts Extracapsular Extension and Tumor Volume". J. Urol. 180 (5): 1975. doi:10.1016/j.juro.2008.07.060. PMID 18801539.
  13. ↑ Progensa PCA3 test - Gen-probe. Retrieved October 1, 2008.

Further reading

  • Clarke RA, Zhao Z, Guo AY, et al. (2009). Zhang B, ed. "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. PMC 2655648. PMID 19319183. 
  • 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. 
  • 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. 
  • 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. doi:10.1016/S0090-4295(03)00759-3. PMID 14607216. 
  • 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. 
  • 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. 
  • 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. 
  • Hessels D, Schalken JA (2009). "The use of PCA3 in the diagnosis of prostate cancer.". Nature Reviews Urology 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. 
  • 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. 
  • Gandini O, Luci L, Stigliano A, et al. (2003). "Is DD3 a new prostate-specific gene?". Anticancer Res. 23 (1A): 305–8. PMID 12680228. 
  • 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. 
  • 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. 
  • 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. doi:10.3892/ijo.24.5.1085. PMID 15067329. 
  • 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. 
  • 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. doi:10.1016/S0302-2838(03)00201-X. PMID 12814669. 
  • 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. 

External links

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