Potential of miRNAs in urinary extracellular vesicles for management of active surveillance in prostate cancer patients

Br J Cancer. 2022 Feb;126(3):492-501. doi: 10.1038/s41416-021-01598-1. Epub 2021 Nov 22.

Abstract

Background: Active surveillance is an alternative to radical treatment for patients with low-risk prostate cancer, which could also benefit some patients with intermediate risk. We have investigated the use of miRNA in urinary extracellular vesicles to stratify these patients.

Methods: NGS was performed to profile the miRNAs from small urinary extracellular vesicles in a cohort of 70 patients with prostate cancer ISUP Grade 1, 2 or 3. The most promising candidates were then analysed by RT-qPCR in a new cohort of 60 patients.

Results: NGS analysis identified nine miRNAs differentially expressed in at least one of the comparisons. The largest differences were found with miR-1290 (Grade 3 vs. 1), miR-320a-3p (Grade 3 vs. 2) and miR-155-5p (Grade 2 vs. 1). Combinations of 2-3 miRNAs were able to differentiate between two ISUP grades with an AUC 0.79-0.88. RT-qPCR analysis showed a similar trend for miR-186-5p and miR-30e-5p to separate Grade 3 from 2, and miR-320a-3p to separate Grade 2 from 1.

Conclusions: Using NGS, we have identified several miRNAs that discriminate between prostate cancer patients with ISUP Grades 1, 2 and 3. Moreover, miR-186-5p, miR-320a-3p and miR-30e-5p showed a similar behaviour in an independent cohort using an alternative analytical method. Our results show that miRNAs from urinary vesicles can be potentially useful as liquid biopsies for active surveillance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / genetics*
  • Biomarkers, Tumor / urine
  • Extracellular Vesicles / genetics*
  • Extracellular Vesicles / pathology
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / urine*
  • Neoplasm Grading
  • Prostatectomy / methods*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / urine
  • ROC Curve
  • Watchful Waiting / methods*

Substances

  • Biomarkers, Tumor
  • MicroRNAs