Hsa-miR-210-3p expression in breast cancer and its putative association with worse outcome in patients treated with Docetaxel

Sci Rep. 2019 Oct 17;9(1):14913. doi: 10.1038/s41598-019-51581-3.

Abstract

MicroRNA-210-3p is the most prominent hypoxia regulated microRNA, and it has been found significantly overexpressed in different human cancers. We performed the expression analysis of miR-210-3p in a retrospective cohort of breast cancer patients with a median follow-up of 76 months (n = 283). An association between higher levels of miR-210-3p and risk of disease progression (HR: 2.13, 95%CI: 1.33-3.39, P = 0.002) was found in the subgroup of patients treated with Epirubicin and Cyclophosphamide followed by Docetaxel. Moreover, a cut off value of 20.966 established by ROC curve analyses allowed to discriminate patients who developed distant metastases with an accuracy of 85% at 3- (AUC: 0.870, 95%CI: 0.690-1.000) and 83% at 5-years follow up (AUC: 0.832, 95%CI: 0.656-1.000). Whereas the accuracy in discriminating patients who died for the disease was of 79.6% at both 5- (AUC: 0.804, 95%CI: 0.517-1.000) and 10-years (AUC: 0.804. 95%CI: 0.517-1.000) follow-up. In silico analysis of miR-210-3p and Docetaxel targets provided evidence for a putative molecular cross-talk involving microtubule regulation, drug efflux metabolism and oxidative stress response. Overall, our data point to the miR-210-3p involvement in the response to therapeutic regimens including Docetaxel in sequential therapy with anthracyclines, suggesting it may represent a predictive biomarker in breast cancer patients.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / metabolism*
  • Breast / pathology
  • Breast / surgery
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Breast Neoplasms / therapy*
  • Cell Line, Tumor
  • Chemotherapy, Adjuvant / methods
  • Computational Biology
  • Cyclophosphamide / pharmacology
  • Cyclophosphamide / therapeutic use
  • Disease Progression
  • Docetaxel / pharmacology*
  • Docetaxel / therapeutic use
  • Drug Resistance, Neoplasm / genetics*
  • Epirubicin / pharmacology
  • Epirubicin / therapeutic use
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mastectomy
  • MicroRNAs / analysis
  • MicroRNAs / metabolism*
  • Middle Aged
  • Prospective Studies
  • Retrospective Studies

Substances

  • Biomarkers, Tumor
  • MIRN210 microRNA, human
  • MicroRNAs
  • Docetaxel
  • Epirubicin
  • Cyclophosphamide