Exosomal and Non-Exosomal Urinary miRNAs in Prostate Cancer Detection and Prognosis

BACKGROUND MicroRNAs (miRNAs) are non-coding small RNAs, involved in post-transcriptional regulation of many target genes. METHODS Five miRNAs that have been consistently found deregulated in PCa (miR-21, miR-141, miR-214, miR-375, and let-7c) were analyzed in urinary pellets from 60 prostate cancer (PCa) patients and 10 healthy subjects by qRT-PCR. Besides, urinary exosomes were isolated by differential centrifugation and analyzed for those miRNAs. RESULTS Significant upregulation of miR-21, miR-141, and miR-375 was found comparing PCa patients with healthy subjects in urinary pellets, while miR-214 was found significantly downregulated. Regarding urinary exosomes, miR-21 and miR-375 were also significantly upregulated in PCa but no differences were found for miR-141. Significant differences were found for let-7c in PCa in urinary exosomes while no differences were observed in urinary pellets. A panel combining miR-21 and miR-375 is suggested as the best combination to distinguish PCa patients and healthy subjects, with an AUC of 0.872. Furthermore, the association of miRNAs with clinicopathological characteristics was investigated. MiR-141 resulted significantly correlated with Gleason score in urinary pellets and let-7c with clinical stage in urinary exosomes. Additionally, miR-21, miR-141, and miR-214 were found significantly deregulated in intermediate/high-risk PCa versus low-risk/healthy subjects in urinary pellets. Significant differences between both groups were found in urinary exosomes for miR-21, miR-375, and let-7c. CONCLUSIONS These findings suggest that the analysis of miRNAs—especially miRNA-21 and miR-375- in urine could be useful as biomarkers in PCa. Prostate 77: 573–583, 2017. © 2016 Wiley Periodicals, Inc.