MiR-29a is a candidate biomarker of better survival in metastatic high-grade serous carcinoma

Hum Pathol. 2016 Aug:54:74-81. doi: 10.1016/j.humpath.2016.03.010. Epub 2016 Apr 8.

Abstract

The objective of this study was to analyze the clinical role of 9 microRNAs (miRs) previously found to be overexpressed in ovarian carcinoma effusions compared with primary ovarian carcinomas. High-grade serous carcinoma effusions (n=148) were analyzed for expression of miR-29a, miR-31, miR-99b, miR-182, miR-210, miR-221, miR-222, miR-224, and miR-342 using quantitative polymerase chain reaction. Expression levels were analyzed for association with clinicopathological parameters and survival. miR-29a and miR-31 levels were further assessed for association with protein expression of their targets Stathmin and DNA methyltransferase-3A (DNMT3A) by immunohistochemistry and Western blotting, respectively. miRNA levels were unrelated to clinicopathological parameters. However, higher miR-29a levels were significantly related to longer overall survival in univariate (P=.007) and Cox multivariate survival analysis (P=.045). miR-29a levels were inversely related to those of its target DNMT3A (P=.048), and higher DNMT3A expression was significantly related to poor overall survival in univariate (P=.03) and Cox multivariate (P=.016) survival analysis. In contrast, miR-31 levels were directly related to cytoplasmic phospho-Stathmin expression (P=.029) and unrelated to Stathmin and nuclear phospho-Stathmin, and both Stathmin and phospho-Stathmin expressions were unrelated to survival. miR-29a and its target DNMT3A are novel candidate biomarkers of longer and shorter survival, respectively, in metastatic high-grade serous carcinoma.

Keywords: Effusions; High-grade serous carcinoma; MicroRNA; Survival; Targets.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics*
  • DNA (Cytosine-5-)-Methyltransferases / analysis
  • DNA Methyltransferase 3A
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Predisposition to Disease
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Neoplasm Grading
  • Neoplasms, Cystic, Mucinous, and Serous / chemistry
  • Neoplasms, Cystic, Mucinous, and Serous / genetics*
  • Neoplasms, Cystic, Mucinous, and Serous / mortality
  • Neoplasms, Cystic, Mucinous, and Serous / secondary
  • Ovarian Neoplasms / chemistry
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology
  • Phenotype
  • Phosphorylation
  • Proportional Hazards Models
  • Risk Factors
  • Stathmin / analysis
  • Time Factors
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • DNMT3A protein, human
  • MIRN29a microRNA, human
  • MicroRNAs
  • STMN1 protein, human
  • Stathmin
  • DNA (Cytosine-5-)-Methyltransferases
  • DNA Methyltransferase 3A