Global and Targeted miRNA Expression Profiling in Clear Cell Renal Cell Carcinoma Tissues Potentially Links miR-155-5p and miR-210-3p to both Tumorigenesis and Recurrence

Am J Pathol. 2018 Nov;188(11):2487-2496. doi: 10.1016/j.ajpath.2018.07.026. Epub 2018 Sep 8.

Abstract

About 30% of patients undergoing nephrectomy for renal cell carcinoma (RCC) experience disease recurrence. We profiled miRNAs dysregulated in clear-cell (cc) RCC tumor tissues and predictive of recurrence. The expression levels of 800 miRNAs were assessed in paired tumor and normal tissues from a discovery cohort of 18 ccRCC patients. miRNAs found to be differentially expressed were examined in a validation set of 205 patients, using real-time quantitative PCR. Tumor-normal data from 64 patients in The Cancer Genome Atlas were used for external validation. Twenty-eight miRNAs were consistently dysregulated in tumor tissues. On dichotomized analysis, patients with high levels of miR-155-5p and miR-210-3p displayed an increased risk for ccRCC recurrence (hazard ratio, 2.64; 95% CI, 1.49 to 4.70; P = 0.0009; and hazard ratio, 1.80; 95% CI, 1.04 to 3.12; P = 0.036, respectively) and a shorter median recurrence-free survival time than did patients with low levels [P < 0.01 (log rank test)]. A risk score was generated based on the expression levels of miR-155-5p and miR-210-3p, and the trend test was significant (P = 0.005). On pathway analysis, target genes regulated by miR-155-5p and miR-210-3p were mainly enriched in inflammation-related pathways. We identified and validated multiple miRNAs dysregulated in ccRCC tissues; miR-155-5p and miR-210-3p were predictive of ccRCC recurrence, pointing to potential utility as biomarkers and underlying biological mechanisms.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics
  • Carcinogenesis / pathology*
  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / secondary*
  • Case-Control Studies
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoplasm Recurrence, Local / genetics
  • Neoplasm Recurrence, Local / pathology*
  • Prognosis
  • Survival Rate

Substances

  • Biomarkers, Tumor
  • MIRN155 microRNA, human
  • MIRN210 microRNA, human
  • MicroRNAs