PCA3

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.[3][4] Because of its restricted expression profile, the PCA3 RNA is useful as a tumor marker.[5]

PCA3
Identifiers
AliasesPCA3, DD3, NCRNA00019, PCAT3, prostate cancer associated 3 (non-protein coding), prostate cancer associated 3, PRUNE2-AS1
External IDsOMIM: 604845 GeneCards: PCA3
Orthologs
SpeciesHumanMouse
Entrez

50652

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Ensembl

ENSG00000225937

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UniProt

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a

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RefSeq (mRNA)

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RefSeq (protein)

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Location (UCSC)Chr 9: 76.69 – 76.86 Mbn/a
PubMed search[2]n/a
Wikidata
View/Edit Human

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.[6]

Compared to serum PSA, PCA3 has a lower sensitivity but a higher specificity and a better positive and negative predictive value.[7] It is independent of prostate volume, whereas PSA is not.[8] It should be measured in the first portion of urine after prostate massage with digital rectal examination.[9]

PCA3 has been shown to be useful to predict the presence of malignancy in men undergoing repeat prostate biopsy.[9][10] 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.[11]

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.[12][13][14]

Society and culture

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. In April 2012, Hologic bought Gen-Probe for $3.75 billion by cash.[15]

Discovery

PCA3 was discovered to be highly expressed by prostate cancer cells in 1999.[3]

References
  1. GRCh38: Ensembl release 89: ENSG00000225937 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. Bussemakers MJ, van Bokhoven A, Verhaegh GW, Smit FP, Karthaus HF, Schalken JA, Debruyne FM, Ru N, Isaacs WB (December 1999). "DD3: a new prostate-specific gene, highly overexpressed in prostate cancer". Cancer Research. 59 (23): 5975–9. PMID 10606244.
  4. Neves AF, Araújo TG, Biase WK, Meola J, Alcântara TM, Freitas DG, Goulart LR (October 2008). "Combined analysis of multiple mRNA markers by RT-PCR assay for prostate cancer diagnosis". Clinical Biochemistry. 41 (14–15): 1191–8. doi:10.1016/j.clinbiochem.2008.06.013. PMID 18640109.
  5. Loeb S (November 2008). "Does PCA3 help identify clinically significant prostate cancer?". European Urology. 54 (5): 980–1. doi:10.1016/j.eururo.2008.07.027. PMID 18684556.
  6. Laxman B, Morris DS, Yu J, Siddiqui J, Cao J, Mehra R, Lonigro RJ, Tsodikov A, Wei JT, Tomlins SA, Chinnaiyan AM (February 2008). "A first-generation multiplex biomarker analysis of urine for the early detection of prostate cancer". Cancer Research. 68 (3): 645–9. doi:10.1158/0008-5472.CAN-07-3224. PMC 2998181. PMID 18245462.
  7. Vlaeminck-Guillem V, Ruffion A, Andre J (May 2008). "[Value of urinary PCA3 test for prostate cancer diagnosis]". Progres en Urologie (in French). 18 (5): 259–65. doi:10.1016/j.purol.2008.03.029. PMID 18538269.
  8. Deras IL, Aubin SM, Blase A, Day JR, Koo S, Partin AW, Ellis WJ, Marks LS, Fradet Y, Rittenhouse H, Groskopf J (April 2008). "PCA3: a molecular urine assay for predicting prostate biopsy outcome". The Journal of Urology. 179 (4): 1587–92. doi:10.1016/j.juro.2007.11.038. PMID 18295257.
  9. Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, Huland H, Abbou CC, Remzi M, Tinzl M, Feyerabend S, Stillebroer AB, van Gils MP, Schalken JA (November 2008). "Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy". European Urology. 54 (5): 1081–8. doi:10.1016/j.eururo.2008.06.071. PMID 18602209.
  10. Marks LS, Fradet Y, Deras IL, Blase A, Mathis J, Aubin SM, Cancio AT, Desaulniers M, Ellis WJ, Rittenhouse H, Groskopf J (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.
  11. de la Taille A (September 2007). "Progensa PCA3 test for prostate cancer detection". Expert Review of Molecular Diagnostics. 7 (5): 491–7. doi:10.1586/14737159.7.5.491. PMID 17892357. S2CID 11338727.
  12. Nakanishi H, Groskopf J, Fritsche HA, Bhadkamkar V, Blase A, Kumar SV, Davis JW, Troncoso P, Rittenhouse H, Babaian RJ (May 2008). "PCA3 molecular urine assay correlates with prostate cancer tumor volume: implication in selecting candidates for active surveillance". The Journal of Urology. 179 (5): 1804–9, discussion 1809–10. doi:10.1016/j.juro.2008.01.013. PMID 18353398.
  13. van Gils MP, Hessels D, Hulsbergen-van de Kaa CA, Witjes JA, Jansen CF, Mulders PF, Rittenhouse HG, Schalken JA (August 2008). "Detailed analysis of histopathological parameters in radical prostatectomy specimens and PCA3 urine test results". The Prostate. 68 (11): 1215–22. doi:10.1002/pros.20781. PMID 18500693. S2CID 38697285.
  14. Whitman EJ, Groskopf J, Ali A, Chen Y, Blase A, Furusato B, Petrovics G, Ibrahim M, Elsamanoudi S, Cullen J, Sesterhenn IA, Brassell S, Rittenhouse H, Srivastava S, McLeod DG (November 2008). "PCA3 score before radical prostatectomy predicts extracapsular extension and tumor volume". The Journal of Urology. 180 (5): 1975–8, discussion 1978–9. doi:10.1016/j.juro.2008.07.060. PMID 18801539.
  15. Soyoung Kim and Anand Basu (30 April 2012). "Hologic to buy Gen-Probe for $3.75 billion". Reuters. Retrieved April 8, 2017.

Further reading
  • Clarke RA, Zhao Z, Guo AY, Roper K, Teng L, Fang ZM, Samaratunga H, Lavin MF, Gardiner RA (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. Bibcode:2009PLoSO...4.4995C. doi:10.1371/journal.pone.0004995. PMC 2655648. PMID 19319183.
  • Schilling D, Hennenlotter J, Munz M, Bökeler U, Sievert KD, Stenzl A (2010). "Interpretation of the prostate cancer gene 3 in reference to the individual clinical background: implications for daily practice". Urologia Internationalis. 85 (2): 159–65. doi:10.1159/000314078. PMID 20424427. S2CID 25474345.
  • Day JR, Jost M, Reynolds MA, Groskopf J, Rittenhouse H (February 2011). "PCA3: from basic molecular science to the clinical lab". Cancer Letters. 301 (1): 1–6. doi:10.1016/j.canlet.2010.10.019. PMID 21093148.
  • Schalken JA, Hessels D, Verhaegh G (November 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, Blase A, Rittenhouse H, Pollock BH, Tangen C, Parekh D, Leach RJ, Thompson I (October 2008). "Predicting prostate cancer risk through incorporation of prostate cancer gene 3". The Journal of Urology. 180 (4): 1303–8, discussion 1308. doi:10.1016/j.juro.2008.06.038. PMID 18707724.
  • Roobol MJ, Schröder FH, van Leeuwen P, Wolters T, van den Bergh RC, van Leenders GJ, Hessels D (October 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". European Urology. 58 (4): 475–81. doi:10.1016/j.eururo.2010.06.039. PMID 20637539.
  • Sokoll LJ, Ellis W, Lange P, Noteboom J, Elliott DJ, Deras IL, Blase A, Koo S, Sarno M, Rittenhouse H, Groskopf J, Vessella RL (March 2008). "A multicenter evaluation of the PCA3 molecular urine test: pre-analytical effects, analytical performance, and diagnostic accuracy". Clinica Chimica Acta; International Journal of Clinical Chemistry. 389 (1–2): 1–6. doi:10.1016/j.cca.2007.11.003. PMID 18061575.
  • Hessels D, Schalken JA (May 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. S2CID 23967596.
  • Salagierski M, Verhaegh GW, Jannink SA, Smit FP, Hessels D, Schalken JA (January 2010). "Differential expression of PCA3 and its overlapping PRUNE2 transcript in prostate cancer". The Prostate. 70 (1): 70–8. doi:10.1002/pros.21040. PMID 19760627. S2CID 184047.
  • Haese A, de la Taille A, van Poppel H, Marberger M, Stenzl A, Mulders PF, Huland H, Abbou CC, Remzi M, Tinzl M, Feyerabend S, Stillebroer AB, van Gils MP, Schalken JA (November 2008). "Clinical utility of the PCA3 urine assay in European men scheduled for repeat biopsy". European Urology. 54 (5): 1081–8. doi:10.1016/j.eururo.2008.06.071. PMID 18602209.
  • Gandini O, Luci L, Stigliano A, Lucera R, Di Silverio F, Toscano V, Cardillo MR (2003). "Is DD3 a new prostate-specific gene?". Anticancer Research. 23 (1A): 305–8. PMID 12680228.
  • Hessels D, van Gils MP, van Hooij O, Jannink SA, Witjes JA, Verhaegh GW, Schalken JA (January 2010). "Predictive value of PCA3 in urinary sediments in determining clinico-pathological characteristics of prostate cancer". The Prostate. 70 (1): 10–6. doi:10.1002/pros.21032. PMID 19708043. S2CID 10279329.
  • Klecka J, Holubec L, Pesta M, Topolcan O, Hora M, Eret V, Finek J, Chottova-Dvorakova M, Babjuk M, Novak K, Stolz J (February 2010). "Differential display code 3 (DD3/PCA3) in prostate cancer diagnosis". Anticancer Research. 30 (2): 665–70. PMID 20332487.
  • Thelen P, Burfeind P, Grzmil M, Voigt S, Ringert RH, Hemmerlein B (May 2004). "cDNA microarray analysis with amplified RNA after isolation of intact cellular RNA from neoplastic and non-neoplastic prostate tissue separated by laser microdissections". International Journal of Oncology. 24 (5): 1085–92. doi:10.3892/ijo.24.5.1085. PMID 15067329.
  • Tao Z, Shen M, Zheng Y, Mao X, Chen Z, Yin Y, Yu K, Weng Z, Xie H, Li C, Wu X, Hu Y, Zhang X, Wang O, Song Q, Yu Z (August 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". Experimental and Molecular Pathology. 89 (1): 58–62. doi:10.1016/j.yexmp.2010.01.008. PMID 20114043.
  • Hessels D, Klein Gunnewiek JM, van Oort I, Karthaus HF, van Leenders GJ, van Balken B, Kiemeney LA, Witjes JA, Schalken JA (July 2003). "DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer". European Urology. 44 (1): 8–15, discussion 15–6. doi:10.1016/S0302-2838(03)00201-X. PMID 12814669.
  • Mearini E, Antognelli C, Del Buono C, Cochetti G, Giannantoni A, Nardelli E, Talesa VN (June 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. S2CID 7022529.
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