title: Evaluation of a short RNA within Prostate Cancer Gene 3 in the predictive role for future cancer using non-malignant prostate biopsies.
abstract: BACKGROUND
  Prostate Cancer 3 (PCA3) is a long non-coding RNA (ncRNA) upregulated in prostate cancer (PCa). We recently identified a short ncRNA expressed from intron 1 of PCA3. Here we test the ability of this ncRNA to predict the presence of cancer in men with a biopsy without PCa.
  
  
  METHODS
  We selected men whose initial biopsy did not identify PCa and selected matched cohorts whose subsequent biopsies revealed PCa or benign tissue. We extracted RNA from the initial biopsy and measured PCA3-shRNA2, PCA3 and PSA (qRT-PCR).
  
  
  RESULTS
  We identified 116 men with and 94 men without an eventual diagnosis of PCa in 2-5 biopsies (mean 26 months), collected from 2002-2008. The cohorts were similar for age, PSA and surveillance period. We detected PSA and PCA3-shRNA2 RNA in all samples, and PCA3 RNA in 90% of biopsies. The expression of PCA3 and PCA3-shRNA2 were correlated (Pearson's r = 0.37, p<0.01). There was upregulation of PCA3 (2.1-fold, t-test p = 0.02) and PCA3-shRNA2 (1.5-fold) in men with PCa on subsequent biopsy, although this was not significant for the latter RNA (p = 0.2). PCA3 was associated with the future detection of PCa (C-index 0.61, p = 0.01). This was not the case for PCA3-shRNA2 (C-index 0.55, p = 0.2).
  
  
  CONCLUSIONS
  PCA3 and PCA3-shRNA2 expression are detectable in historic biopsies and their expression is correlated suggesting co-expression. PCA3 expression was upregulated in men with PCa diagnosed at a future date, the same did not hold for PCA3-shRNA2. Futures studies should explore expression in urine and look at a time course between biopsy and PCa detection.
authors.affiliation: Academic Urology Unit and Academic Unit of Molecular Oncology, Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Karl H
authors.initials: KH
authors.lastname: Pang
authors.affiliation: Academic Urology Unit and Academic Unit of Molecular Oncology, Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, United Kingdom.
authors.forename: Derek J
authors.initials: DJ
authors.lastname: Rosario
authors.affiliation: Department of Histopathology, Royal Hallamshire Hospital, Sheffield, United Kingdom.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morgan
authors.affiliation: Academic Urology Unit and Academic Unit of Molecular Oncology, Department of Oncology and Human Metabolism, University of Sheffield, Sheffield, United Kingdom.
authors.forename: James W F
authors.initials: JW
authors.lastname: Catto
mesh_terms: D000951:Antigens, Neoplasm / Q000235:genetics* / Q000502:physiology; D001706:Biopsy; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000473:pathology*; D011471:Prostatic Neoplasms / Q000235:genetics*; D058727:RNA, Small Untranslated / Q000235:genetics* / Q000502:physiology; D059467:Transcriptome
chemical_list: D000951:Antigens, Neoplasm; D058727:RNA, Small Untranslated; C479341:prostate cancer antigen 3, human