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

Prostate. 2017 May;77(6):573-583. doi: 10.1002/pros.23295. Epub 2016 Dec 19.

Abstract

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.

Keywords: exosomes; miRNA; prostate cancer; urine.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / urine*
  • Exosomes / genetics
  • Exosomes / metabolism*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / urine*
  • Middle Aged
  • Prognosis
  • Prostatic Neoplasms / diagnosis*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / urine*

Substances

  • Biomarkers, Tumor
  • MicroRNAs