title: Urinary miR-183 and miR-205 do not surpass PCA3 in urine as predictive markers for prostate biopsy outcome despite their highly dysregulated expression in prostate cancer tissue.
abstract: BACKGROUND
  MicroRNAs (miRNAs) have shown to be promising novel biomarkers in various cancers. We aimed to translate the results of an own previous tissue-based miRNA profile of prostate carcinoma (PCa) with upregulated miR-183 and downregulated miR-205 into a urine-based testing procedure for diagnosis of PCa.
  
  
  METHODS
  Urine sediments were prepared from urine samples collected after a standardized digital-rectal examination (DRE) of patients undergoing prostate biopsy with PSA (prostate-specific antigen) values <20 μg/L in consecutive order. According to the sample-size calculation (α=0.05, power=0.95), 38 patients each with PCa and without PCa were randomly enrolled in this study. PCA3 (prostate cancer associated 3) in urine as Food and Drug Administration-approved assay was determined as reference standard for comparison. The miRNAs were measured by RT-qPCR using TaqMan assays and normalized using different approaches.
  
  
  RESULTS
  Both miRNAs were correlated to the mRNA PSA concentrations in the sediments indicating a relationship to the released prostate cells after DRE. However, they had no discriminating capacity between patients with and without PCa. In contrast, PCA3 clearly differentiated between these two patients groups. There was also no significant correlation between miRNAs and standard clinicopathologic variables like Gleason score and serum PSA.
  
  
  CONCLUSIONS
  The data of our study show that miR-183 and miR-205 failed to detect early and aggressive PCa despite their highly dysregulated expression in cancer tissue. Our results and the critical evaluation of the few data of other studies raise serious doubts concerning the capability of urinary miRNAs to replace or improve PCA3 as predictive marker for prostate biopsy outcome.
authors.forename: Carsten
authors.initials: C
authors.lastname: Stephan
authors.forename: Monika
authors.initials: M
authors.lastname: Jung
authors.forename: Silke
authors.initials: S
authors.lastname: Rabenhorst
authors.forename: Ergin
authors.initials: E
authors.lastname: Kilic
authors.forename: Klaus
authors.initials: K
authors.lastname: Jung
mesh_terms: D000368:Aged; D000951:Antigens, Neoplasm / Q000235:genetics / Q000652:urine*; D014408:Biomarkers, Tumor / Q000235:genetics / Q000652:urine; D001706:Biopsy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000652:urine*; D008875:Middle Aged; D011379:Prognosis; D011467:Prostate / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology* / Q000652:urine*; D012015:Reference Standards
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor; D035683:MicroRNAs; D017430:Prostate-Specific Antigen; C533449:MIRN183 microRNA, human; C534425:MIR205, human; C479341:prostate cancer antigen 3, human