Stromal expression of MiR-21 predicts biochemical failure in prostate cancer patients with Gleason score 6

PLoS One. 2014 Nov 17;9(11):e113039. doi: 10.1371/journal.pone.0113039. eCollection 2014.

Abstract

Aim: microRNAs (miRNAs) are involved in various neoplastic diseases, including prostate cancer (PCs). The aim of this study was to investigate the miRNA profile in PC tissue, to assess their association with clinicopathologic data, and to evaluate the potential of miRNAs as diagnostic and prognostic markers.

Materials and methods: From a cohort of 535 patients submitted to radical prostatectomy (RP), a sample of 30 patients (14 patients with rapid biochemical failure (BF) and 16 patients without BF) with Gleason score 7 were analyzed. A total of 1435 miRNAs were quantified by microarray hybridization, and selected miRNAs with the highest Standard deviation (n = 50) were validated by real-time quantitative PCR (qRT-PCR). In situ hybridization (ISH) was used to evaluate the expression of miR-21.

Results: miR-21 was the only miR that was significantly up-regulated in the BF group (p = 0.045) miR-21 was up-regulated in patients with BF compared with non-BF group (p = 0.05). In univariate analyses, high stromal expression of miR-21 had predictive impact on biochemical failure-free survival (BFFS) and clinical failure-free survival (CFFS) (p = 0.006 and p = 0.04, respectively). In the multivariate analysis, high stromal expression of miR-21 expression was found to be an independent prognostic factor for BFFS in patients with Gleason score 6 (HR 2.41, CI 95% 1.06-5.49, p = 0.037).

Conclusion: High stromal expression of miR-21 was associated with poor biochemical recurrence-free survival after RP. For patients with Gleason score 6, miR-21 may help predict the risk of future disease progression and thereby help select patients for potential adjuvant treatment or a more stringent follow-up.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Biomarkers, Tumor / genetics*
  • Cohort Studies
  • Disease Progression
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / mortality
  • Neoplasm Staging
  • Prognosis
  • Prostatectomy
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / mortality
  • Prostatic Neoplasms / pathology*
  • Prostatic Neoplasms / surgery
  • Real-Time Polymerase Chain Reaction
  • Stromal Cells / metabolism
  • Stromal Cells / pathology*
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MIRN21 microRNA, human
  • MicroRNAs

Grants and funding

This study was supported by grants from Helse Nord, The Northern Health Administration (www.helse-nord.no) and University of Tromsø Arctic University of Norway (www.uit.no). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.