Diagnostic and Prognostic MicroRNA Biomarkers for Prostate Cancer in Cell-free Urine

Eur Urol Focus. 2018 Dec;4(6):825-833. doi: 10.1016/j.euf.2017.02.018. Epub 2017 Mar 9.

Abstract

Background: Widespread use of prostate-specific antigen (PSA) testing for prostate cancer (PC) detection has led to extensive overdiagnosis and overtreatment. Urine-based microRNA (miRNA) biomarkers could be useful in PC diagnosis and prognosis.

Objective: To train and validate urine-based microRNA (miRNA) biomarkers that may assist in PC diagnosis and prognosis.

Design, setting, and participants: We profiled the expression levels of 92 miRNAs via reverse transcriptase-poymerase chain reaction in cell-free urine samples from 29 patients with benign prostatic hyperplasia (BPH) and 215 patients with clinically localized PC (cohort 1). Our findings were validated in an independent cohort of 29 BPH patients and 220 patients with clinically localized PC (cohort 2).

Results and limitations: We identified and validated several deregulated miRNAs in urine samples from PC patients. In addition, we trained a novel diagnostic three-miRNA model (miR-222-3p*miR-24-3p/miR-30c-5p) that distinguished BPH and PC patients with an area under the curve (AUC) of 0.95 in cohort 1, and was successfully validated in cohort 2 (AUC 0.89). Furthermore, we trained a novel prognostic three-miRNA model (miR-125b-5p*let-7a-5p/miR-151-5p) that predicted time to biochemical recurrence after radical prostatectomy independently of routine clinicopathological parameters in cohort 1, and was successfully validated in cohort 2.

Conclusions: Future clinical implementation of our novel diagnostic and prognostic three-miRNA signatures could help in primary diagnosis of PC and guide treatment decisions. Further validation studies are warranted.

Patient summary: Using two large patient cohorts, we searched for novel prostate cancer biomarkers in urine. We found two new sets of microRNA biomarkers in urine that could accurately predict the presence of prostate cancer and the likelihood of recurrence after prostatectomy. Further studies are needed before an actual clinical test can be developed.

Keywords: Biomarker; Diagnosis; MicroRNA; Prognosis; Prostate cancer; Urine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Area Under Curve
  • Biomarkers, Tumor / urine*
  • Case-Control Studies
  • Disease-Free Survival
  • Humans
  • Kallikreins / blood
  • Male
  • MicroRNAs / urine*
  • Middle Aged
  • Neoplasm Recurrence, Local / blood
  • Neoplasm Recurrence, Local / epidemiology*
  • Prognosis
  • Prostate-Specific Antigen / blood
  • Prostatectomy
  • Prostatic Hyperplasia / diagnosis
  • Prostatic Hyperplasia / urine
  • Prostatic Neoplasms / diagnosis
  • Prostatic Neoplasms / surgery
  • Prostatic Neoplasms / urine*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Time Factors

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Kallikreins
  • kallikrein-related peptidase 3, human
  • Prostate-Specific Antigen