PCA3

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PCA3
Identifiers
Aliases PCA3 , DD3, NCRNA00019, PCAT3, prostate cancer associated 3 (non-protein coding), prostate cancer associated 3, PRUNE2-AS1
External IDs OMIM: 604845 GeneCards: PCA3
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

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RefSeq (protein)

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

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]

Contents

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.[ citation needed ] Gen-Probe acquired rights to the PCA3 test from Diagnocure in 2003.[ citation needed ] 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] [ third-party source needed ]

Related Research Articles

Prostate Gland of the male reproductive system in most mammals

The prostate is both an accessory gland of the male reproductive system and a muscle-driven mechanical switch between urination and ejaculation. It is found only in some mammals. It differs between species anatomically, chemically, and physiologically. Anatomically, the prostate is found below the bladder, with the urethra passing through it. It is described in gross anatomy as consisting of lobes, and in microanatomy by zone. It is surrounded by an elastic, fibromuscular capsule and contains glandular tissue as well as connective tissue.

Prostate cancer Male reproductive organ cancer

Prostate cancer is cancer of the prostate. The prostate is a gland in the male reproductive system that surrounds the urethra just below the bladder. Most prostate cancers are slow growing. Cancerous cells may spread to other areas of the body, particularly the bones and lymph nodes. It may initially cause no symptoms. In later stages, symptoms include pain or difficulty urinating, blood in the urine, or pain in the pelvis or back. Benign prostatic hyperplasia may produce similar symptoms. Other late symptoms include fatigue, due to low levels of red blood cells.

Bladder cancer Urinary system cancer that begins in the urinary bladder

Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become malignant.

Prostate-specific antigen

Prostate-specific antigen (PSA), also known as gamma-seminoprotein or kallikrein-3 (KLK3), P-30 antigen, is a glycoprotein enzyme encoded in humans by the KLK3 gene. PSA is a member of the kallikrein-related peptidase family and is secreted by the epithelial cells of the prostate gland.

Prostate biopsy

Prostate biopsy is a procedure in which small hollow needle-core samples are removed from a man's prostate gland to be examined for the presence of prostate cancer. It is typically performed when the result from a PSA blood test is high. It may also be considered advisable after a digital rectal exam (DRE) finds possible abnormality. PSA screening is controversial as PSA may become elevated due to non-cancerous conditions such as benign prostatic hyperplasia (BPH), by infection, or by manipulation of the prostate during surgery or catheterization. Additionally many prostate cancers detected by screening develop so slowly that they would not cause problems during a man's lifetime, making the complications due to treatment unnecessary.

Prostatic acid phosphatase

Prostatic acid phosphatase (PAP), also prostatic specific acid phosphatase (PSAP), is an enzyme produced by the prostate. It may be found in increased amounts in men who have prostate cancer or other diseases.

Prostate cancer screening is the screening process used to detect undiagnosed prostate cancer in men without signs or symptoms. When abnormal prostate tissue or cancer is found early, it may be easier to treat and cure, but it is unclear if early detection reduces mortality rates.

Early prostate cancer antigen-2 (EPCA-2) is a protein of which blood levels are elevated in prostate cancer. It appears to provide more accuracy in identifying early prostate cancer than the standard prostate cancer marker, PSA.

KLK4

Kallikrein-related peptidase 4 is a protein which in humans is encoded by the KLK4 gene.

EN2 (gene)

Homeobox protein engrailed-2 is a protein that in humans is encoded by the EN2 gene. It is a member of the engrailed gene family.

KLK11

Kallikrein-11 is a protein that in humans is encoded by the KLK11 gene.

KLK15

Kallikrein-15 is a protein that in humans is encoded by the KLK15 gene.

UGT2B17

UDP-glucuronosyltransferase 2B17 is an enzyme that in humans is encoded by the UGT2B17 gene.

Enzalutamide

Enzalutamide, sold under the brand name Xtandi, is a nonsteroidal antiandrogen (NSAA) medication which is used in the treatment of prostate cancer. It is indicated for use in conjunction with castration in the treatment of metastatic castration-resistant prostate cancer (mCRPC), nonmetastatic castration-resistant prostate cancer, and metastatic castration-sensitive prostate cancer (mCSPC). It is taken by mouth.

Douglas S. Scherr, M.D. is an American surgeon and specialist in Urologic Oncology. He is currently the Clinical Director of Urologic Oncology at the Weill Medical College of Cornell University in New York City. He also holds an appointment at the Rockefeller University in New York as a Visiting Associate Physician. Dr. Scherr was the first physician at Cornell to perform a robotic prostatectomy as well as a robotic cystectomy.

Simon J. Hall, M.D., is the Associate Professor and Kyung Hyun Kim, M.D. Chair of Urology and Assistant Professor, Department of Gene and Cell Medicine at The Mount Sinai School of Medicine, as well as the Director of the Barbara and Maurice Deane Prostate Health and Research Center at The Mount Sinai Medical Center, both in New York City.

Active surveillance of prostate cancer

Active surveillance is a management option for localized prostate cancer that can be offered to appropriate patients who would also be candidates for aggressive local therapies, with the intent to intervene if the disease progresses. Active surveillance should not be confused with watchful waiting, another observational strategy for men that would not be candidates for curative therapy because of a limited life expectancy. Active surveillance offers men with a prostate cancer that is thought to have a low risk of causing harm in the absence of treatment, a chance to delay or avoid aggressive treatment and its associated side effects.While prostate cancer is the most common non cutaneous cancer and second leading cause of cancer-related death in American men, it is conservatively estimated that approximately 100,000 men per year in the United States who would be eligible for conservative treatment through active surveillance, undergo unnecessary treatments. The management of localized prostate cancer is controversial and men with localized disease diagnosed today often undergo treatments with significant side effects that will not improve overall health outcomes. The 2011 NIH State-of-the-Science Conference Statement on the "Role of active surveillance in the management of men with localized prostate cancer" pointed out the many unanswered questions about observational strategies for prostate cancer that require further research and clarification. These included:

Cancer biomarker Substance or process that is indicative of the presence of cancer in the body

A cancer biomarker refers to a substance or process that is indicative of the presence of cancer in the body. A biomarker may be a molecule secreted by a tumor or a specific response of the body to the presence of cancer. Genetic, epigenetic, proteomic, glycomic, and imaging biomarkers can be used for cancer diagnosis, prognosis, and epidemiology. Ideally, such biomarkers can be assayed in non-invasively collected biofluids like blood or serum.

PI-RADS is an acronym for Prostate Imaging Reporting and Data System, defining standards of high quality clinical service for multi-parametric Magnetic Resonance Imaging (mpMRI), including image creation and reporting.

Prognostic markers are biomarkers used to measure the progress of a disease in the patient sample. Prognostic markers are useful to stratify the patients into groups, guiding towards precise medicine discovery. The widely used prognostic markers in cancers include stage, size, grade, node and metastasis. In addition to these common markers, there are prognostic markers specific to different cancer types. For example estrogen level, progesterone and HER2 are markers specific to breast cancer patients. There is evidence showing that genes behaving as tumor suppressors or carcinogens could act as prognostic markers due to altered gene expression or mutation. Besides genetic biomarkers, there are also biomarkers that are detected in plasma or body fluid which can be metabolic or protein biomarkers.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000225937 - Ensembl, May 2017
  2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  3. 1 2 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. 1 2 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