The BRCA1/2-directed miRNA signature predicts a good prognosis in ovarian cancer patients with wild-type BRCA1/2

Oncotarget. 2015 Feb 10;6(4):2397-406. doi: 10.18632/oncotarget.2963.

Abstract

Ovarian cancer patients carrying alterations (i.e., germline mutations, somatic mutations, hypermethylations and/or deletions) of BRCA1 or BRCA2 (BRCA1/2) have a better prognosis than BRCA1/2 alteration non-carriers. However, patients with wild-type BRCA1/2 may also have a favorable prognosis as a result of other mechanisms that remain poorly elucidated, such as the deregulation of miRNAs. We therefore sought to identify BRCA1/2-directed miRNA signatures that have prognostic value in ovarian cancer patients with wild-type BRCA1/2 and study how the deregulation of miRNAs impacts the prognosis of patients treated with platinum-based chemotherapy. By analyzing multidimensional datasets of ovarian cancer patients from the TCGA data portal, we identified three miRNAs (hsa-miR-146a, hsa-miR-148a and hsa-miR-545) that target BRCA1/2 and were associated with overall survival and progression-free survival in patients with wild-type BRCA1/2. By analyzing the expression profiles and Gene Ontology functional enrichment, we found that carriers of BRCA1/2 alterations and patients with miRNA deregulation shared a common mechanism, regulation of the DNA repair-related pathways, that affects the prognosis of ovarian cancer patients. Our work highlights that a proportion of patients with wild-type BRCA1/2 ovarian cancers benefit from platinum-based chemotherapy and that the patients who benefit could be predicted from BRCA1/2-directed miRNA signature.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • BRCA1 Protein / genetics*
  • BRCA2 Protein / genetics*
  • Disease-Free Survival
  • Female
  • Gene Expression Profiling / statistics & numerical data
  • Gene Expression Regulation, Neoplastic / drug effects
  • Genotype
  • Humans
  • MicroRNAs / genetics*
  • Middle Aged
  • Multivariate Analysis
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics*
  • Platinum / administration & dosage
  • Prognosis
  • Proportional Hazards Models

Substances

  • BRCA1 Protein
  • BRCA2 Protein
  • MIR545 microRNA, human
  • MIRN146 microRNA, human
  • MIRN148 microRNA, human
  • MicroRNAs
  • Platinum