Expression of miR-100 and miR-138 as prognostic biomarkers in non-muscle-invasive bladder cancer

APMIS. 2019 Aug;127(8):545-553. doi: 10.1111/apm.12973.

Abstract

microRNA alterations are involved in bladder cancer tumorigenesis. The aim of the current study was to evaluate the potential role of miR-100 and miR-138 as prognostic biomarkers in Ta/T1 non-muscle-invasive bladder cancer (NMIBC). We assessed a quantitative RT-PCR analysis of miR-100 and miR-138 in 50 bladder tumor samples (stage Ta/T1) and four healthy adjacent tissues. Western blot analysis was used to measure protein expression of FGFR3 and cyclin D3 in order to know whether these targets can be regulated by miR-100 and miR-138, respectively. The statistical analysis included non-parametric tests (Mann-Whitney U and Kruskal-Wallis) and univariate survival analysis by Kaplan-Meier method and the log-rank test. Low expression of miR-138 characterized recurrent tumors (p = 0.043), and higher expression levels were associated with longer recurrence-free survival (p = 0.012). However, low miR-100 expression correlated with longer progression-free survival (marginal significance; p = 0.053) and cancer-specific overall survival (p = 0.006). Additionally, higher levels of miR-100 were associated with negative FGFR3 protein expression (p = 0.032) and higher levels of miR-138 were associated with positive cyclin D3 protein expression (p = 0.037). Our results support miR-138 and miR-100 as prognostic biomarkers in patients with NMIBC.

Keywords: bladder cancer; microRNA expression; prognostic biomarkers; stage Ta/T1.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Case-Control Studies
  • Female
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Staging
  • Prognosis
  • Real-Time Polymerase Chain Reaction
  • Receptor, Fibroblast Growth Factor, Type 3 / genetics*
  • Survival Analysis
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / pathology

Substances

  • Biomarkers, Tumor
  • MIRN100 microRNA, human
  • MIRN138 microRNA, human
  • MicroRNAs
  • FGFR3 protein, human
  • Receptor, Fibroblast Growth Factor, Type 3