title: Identification of miR-187 and miR-182 as biomarkers of early diagnosis and prognosis in patients with prostate cancer treated with radical prostatectomy.
abstract: OBJECTIVE
  miRNAs are noncoding RNAs that negatively regulate target mRNA gene expression. Aberrant miRNA expression is associated with prostate cancer pathogenesis. We identified miRNAs as potential biomarkers for prostate cancer diagnosis and prognosis.
  
  
  METHODS
  Total RNA was obtained from 10 normal prostate and 50 prostate cancer samples, and analyzed using the GeneChip® miRNA 2.0 Array. At a median followup of 92 months (range 2 to 189) an independent cohort of 273 paraffin embedded prostate cancer samples was used for validation by quantitative reverse transcriptase-polymerase chain reaction. Another 92 urine samples from patients undergoing prostate biopsy were evaluated for these miRNAs.
  
  
  RESULTS
  miR-182 and 187, the miRNAs most differentially expressed between normal and tumor tissue, were selected for further validation. miR-187 inversely correlated with cT (p = 0.125) and pT (p = 0.0002) stages, Gleason score (p = 0.003) and TMPRSS2-ERG status (p = 0.003). The log rank test showed associations of miR-182 with biochemical (p = 0.026) and clinical (p = 0.043) progression-free survival, as also noted on multivariate analysis. A significant independent improvement in the definition of risk of progression was achieved by combining miR-182 expression with Gleason score (p <0.0001). miR-187 detection in urine provided an independent predictive value for positive biopsy. A prediction model including serum prostate specific antigen, urine PCA3 and miR-187 provided 88.6% sensitivity and 50% specificity (AUC 0.711, p = 0.001).
  
  
  CONCLUSIONS
  Results show that miR-182 and 187 are promising biomarkers for prostate cancer prognosis to identify patients at risk for progression and for diagnosis to improve the predictive capability of existing biomarkers.
authors: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Irene
authors: I
authors: Casanova-Salas
authors: Service of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: José
authors: J
authors: Rubio-Briones
authors: Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Ana
authors: A
authors: Calatrava
authors: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors: Caterina
authors: C
authors: Mancarella
authors: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors: Esther
authors: E
authors: Masiá
authors: Service of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Juan
authors: J
authors: Casanova
authors: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Antonio
authors: A
authors: Fernández-Serra
authors: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Luis
authors: L
authors: Rubio
authors: Service of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Miguel
authors: M
authors: Ramírez-Backhaus
authors: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors: Ana
authors: A
authors: Armiñán
authors: Service of Urology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: José
authors: J
authors: Domínguez-Escrig
authors: Department of Statistics, University of Valencia, Valencia, Spain.
authors: Francisco
authors: F
authors: Martínez
authors: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain.
authors: Zaida
authors: Z
authors: García-Casado
authors: Laboratory of Experimental Oncology, Istituto Ortopedico Rizzoli, Bologna, Italy.
authors: Katia
authors: K
authors: Scotlandi
authors: Polymer Therapeutics Laboratory, Centro de Investigación Príncipe Felipe, Valencia, Spain.
authors: María J
authors: MJ
authors: Vicent
authors: Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. Electronic address: jalopez@fivo.org.
authors: José Antonio
authors: JA
authors: López-Guerrero
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000652:urine; D042241:Early Diagnosis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000652:urine; D011379:Prognosis; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000601:surgery* / Q000652:urine; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; C571843:MIRN187 microRNA, human; D035683:MicroRNAs; C538984:Mirn182 microRNA, human
keywords: biological markers; diagnosis; microRNAs; prognosis; prostatic neoplasms