PCA3 and TMPRSS2-ERG gene fusions as diagnostic biomarkers for prostate cancer.

The incidence of prostate cancer (PCa) is rising steadily among males in many countries. Serum prostate-specific antigen (PSA) is widely applied to clinical diagnosis and screening of PCa. However, the so-called grey area of PSA levels 4.0-10.0 ng/mL has a low specificity of 25-40% resulting in a high rate of negative biopsy and overtreatment. So in order to treat PCa patients in early stage, there is an urgent need for new biomarkers in PCa diagnosis. The PCA3 gene, a non-coding RNA (ncRNA) that is highly expressed in prostate cancer (PCa) cells, has been identified as a molecular biomarkers to detect PCa, of which PCA3 has already under clinical application. PCA3 is strongly overexpressed in malignant prostate tissue compared to benign or normal adjacent one. Newly, PCA3 is considered to be a promising biomarker in clinical diagnosis and targeted therapy. The diagnostic significance of PCA3, however, is awaiting further researches. Moreover, it has been demonstrated recently that TMPRSS2-ERG gene fusion is identified as the predominant genetic change in patients diagnosed with PCa. Recent study revealed that combination of the PCA3 and TMPRSS2-ERG gene fusion test optimizes PCa detection compared with that of single biomarker, which would lead to a considerable reduction of the number of prostate biopsies. In this review, we focused on the potential use of PCA3 and TMPRSS2-ERG gene fusion detection in the diagnosis of PCa.

[1]  J. Locke,et al.  Next generation biomarkers in prostate cancer. , 2016, Frontiers in bioscience.

[2]  G. Cigliana,et al.  PCA3 in prostate cancer and tumor aggressiveness detection on 407 high-risk patients: a National Cancer Institute experience , 2015, Journal of Experimental & Clinical Cancer Research.

[3]  D. Bruzzese,et al.  Prostate health index vs percent free prostate-specific antigen for prostate cancer detection in men with "gray" prostate-specific antigen levels at first biopsy: systematic review and meta-analysis. , 2014, Translational research : the journal of laboratory and clinical medicine.

[4]  Jiao Zhang,et al.  Neuroendocrine Prostate Cancer (NEPC) progressing from conventional prostatic adenocarcinoma: factors associated with time to development of NEPC and survival from NEPC diagnosis-a systematic review and pooled analysis. , 2014, Journal of clinical oncology : official journal of the American Society of Clinical Oncology.

[5]  E. Reddy,et al.  Molecular Mechanism of Activation of Transforming Growth Factor Beta/Smads Signaling Pathway in Ets Related Gene-Positive Prostate Cancers. , 2014, Journal of pharmaceutical sciences and pharmacology.

[6]  S. Tomlins Urine PCA3 and TMPRSS2:ERG using cancer-specific markers to detect cancer. , 2014, European urology.

[7]  T. D. de Reijke,et al.  Prospective multicentre evaluation of PCA3 and TMPRSS2-ERG gene fusions as diagnostic and prognostic urinary biomarkers for prostate cancer. , 2014, European urology.

[8]  T. H. van der Kwast,et al.  EAU guidelines on prostate cancer. part 1: screening, diagnosis, and local treatment with curative intent-update 2013. , 2014, European urology.

[9]  G. Palomaki,et al.  Comparative effectiveness review: prostate cancer antigen 3 testing for the diagnosis and management of prostate cancer. , 2013, The Journal of urology.

[10]  T. Miki,et al.  Clinical utility of the prostate cancer gene 3 (PCA3) urine assay in Japanese men undergoing prostate biopsy , 2013, BJU International.

[11]  N. Maitland,et al.  Monoallelic expression of TMPRSS2/ERG in prostate cancer stem cells , 2013, Nature Communications.

[12]  F. Aragona,et al.  Prostate cancer detection rate at repeat saturation biopsy: PCPT risk calculator versus PCA3 score versus case-finding protocol. , 2013, The Canadian journal of urology.

[13]  J. Schalken,et al.  Predicting prostate biopsy outcome using a PCA3-based nomogram in a Polish cohort. , 2013, Anticancer research.

[14]  K. Chevli,et al.  Use of PCA3 in detecting prostate cancer in initial and repeat prostate biopsy patients , 2013, The Prostate.

[15]  M. Caetano,et al.  PCA3 noncoding RNA is involved in the control of prostate-cancer cell survival and modulates androgen receptor signaling , 2012, BMC Cancer.

[16]  Y. Allory,et al.  The value of urinary prostate cancer gene 3 (PCA3) scores in predicting pathological features at radical prostatectomy , 2012, BJU international.

[17]  Jennifer R. Rider,et al.  The TMPRSS2:ERG Rearrangement, ERG Expression, and Prostate Cancer Outcomes: A Cohort Study and Meta-analysis , 2012, Cancer Epidemiology, Biomarkers & Prevention.

[18]  W. Grizzle,et al.  Histone deacetylase inhibitors, valproic acid and trichostatin-A induce apoptosis and affect acetylation status of p53 in ERG-positive prostate cancer cells. , 2011, International journal of oncology.

[19]  W. Schiemann,et al.  Transforming growth factor-β and the hallmarks of cancer. , 2011, Cellular signalling.

[20]  C. Bieberich,et al.  ERG gene rearrangements are common in prostatic small cell carcinomas , 2011, Modern Pathology.

[21]  M. Rubin,et al.  ETS gene fusions in prostate cancer: from discovery to daily clinical practice. , 2009, European urology.

[22]  K. Miller Re: PCA3 Score before Radical Prostatectomy Predicts Extracapsular Extension and Tumor Volume , 2009 .

[23]  R. Shah,et al.  The Discovery of Common Recurrent Transmembrane Protease Serine 2 (TMPRSS2)-Erythroblastosis Virus E26 Transforming Sequence (ETS) Gene Fusions in Prostate Cancer: Significance and Clinical Implications , 2009, Advances in anatomic pathology.

[24]  G. Jenster,et al.  Overexpression of Prostate-Specific TMPRSS2(exon 0)-ERG Fusion Transcripts Corresponds with Favorable Prognosis of Prostate Cancer , 2009, Clinical Cancer Research.

[25]  A. Kuten,et al.  Small Cell (Neuroendocrine) Carcinoma of the Prostate: Etiology, Diagnosis, Prognosis, and Therapeutic Implications—A Retrospective Study of 30 Patients From the Rare Cancer Network , 2008, The American journal of the medical sciences.

[26]  Chen Sun,et al.  Delineation of TMPRSS2-ERG Splice Variants in Prostate Cancer , 2008, Clinical Cancer Research.

[27]  Seongjoon Koo,et al.  PCA3: a molecular urine assay for predicting prostate biopsy outcome. , 2008, The Journal of urology.

[28]  P. Nelson,et al.  A causal role for ERG in neoplastic transformation of prostate epithelium , 2008, Proceedings of the National Academy of Sciences.

[29]  S. Srivastava,et al.  Mapping of TMPRSS2–ERG fusions in the context of multi-focal prostate cancer , 2008, Modern Pathology.

[30]  J. Epstein,et al.  Small Cell Carcinoma of the Prostate: A Morphologic and Immunohistochemical Study of 95 Cases , 2008, The American journal of surgical pathology.

[31]  J. Witjes,et al.  Detection of TMPRSS2-ERG Fusion Transcripts and Prostate Cancer Antigen 3 in Urinary Sediments May Improve Diagnosis of Prostate Cancer , 2007, Clinical Cancer Research.

[32]  M. Wakefield,et al.  Unusual and underappreciated: small cell carcinoma of the prostate. , 2007, Seminars in oncology.

[33]  M. Rubin,et al.  TMPRSS2-ERG Fusion Prostate Cancer: An Early Molecular Event Associated With Invasion , 2006, The American journal of surgical pathology.

[34]  V. Srikantan,et al.  Frequent overexpression of ETS-related gene-1 (ERG1) in prostate cancer transcriptome , 2006, Oncogene.

[35]  Lei Wang,et al.  Noninvasive detection of TMPRSS2:ERG fusion transcripts in the urine of men with prostate cancer. , 2006, Neoplasia.

[36]  Ximing J. Yang,et al.  Small Cell Carcinoma of the Prostate: An Immunohistochemical Study , 2006, The American journal of surgical pathology.

[37]  Arul M Chinnaiyan,et al.  TMPRSS2:ETV4 gene fusions define a third molecular subtype of prostate cancer. , 2006, Cancer research.

[38]  Freddie C Hamdy,et al.  Use of prostate-specific antigen (PSA) isoforms for the detection of prostate cancer in men with a PSA level of 2-10 ng/ml: systematic review and meta-analysis. , 2005, European urology.

[39]  J Alfred Witjes,et al.  DD3(PCA3)-based molecular urine analysis for the diagnosis of prostate cancer. , 2003, European urology.

[40]  M. Sheppard,et al.  Small Cell Lung Carcinoma (SCLC): A Clinicopathologic Study of 100 Cases With Surgical Specimens , 2002, The American journal of surgical pathology.

[41]  William J Catalona,et al.  Serial biopsy results in prostate cancer screening study. , 2002, The Journal of urology.

[42]  C C Schulman,et al.  Optimal predictors of prostate cancer on repeat prostate biopsy: a prospective study of 1,051 men. , 2000, The Journal of urology.

[43]  A. Roberts,et al.  Role of transforming growth factor-beta signaling in cancer. , 2000, Journal of the National Cancer Institute.

[44]  W. Isaacs,et al.  DD3: a new prostate-specific gene, highly overexpressed in prostate cancer. , 1999, Cancer research.

[45]  A. Jemal,et al.  Global cancer statistics , 2011, CA: a cancer journal for clinicians.

[46]  A W Partin,et al.  Disease progression following radical prostatectomy in men with Gleason score 7 tumor. , 1998, The Journal of urology.

[47]  T. Papas,et al.  The erg gene: a human gene related to the ets oncogene. , 1987, Proceedings of the National Academy of Sciences of the United States of America.

[48]  T. Papas,et al.  erg, a human ets-related gene on chromosome 21: alternative splicing, polyadenylation, and translation. , 1987, Science.