Effect of radiotherapy on the expression of cardiovascular disease-related miRNA-146a, -155, -221 and -222 in blood of women with breast cancer

PLoS One. 2019 May 31;14(5):e0217443. doi: 10.1371/journal.pone.0217443. eCollection 2019.

Abstract

Breast cancer (BC) is one of the most important neoplasias among women. Many patients receive radiotherapy (RT), which involves radiation exposure of the thoracic zone, including the heart and blood vessels, leading to the development of cardiovascular disease (CVD) as a long-term side effect. The severity of CVD-related pathologies leads research on assessing novel CVD biomarkers as diagnostic, prognostic or therapeutic agents. Currently, the possible candidates include blood microRNAs (miRNAs). Previous studies have supported a role for miRNA-146a, -155, -221, and -222 in the progression of CVD. Our purpose was to evaluate the RT-induced modulation of the expression of these miRNAs in the blood of women with BC. Pre-RT control and post-RT blood samples were collected, and after miRNA isolation and reverse transcription, the levels of the selected miRNAs were measured by real-time PCR. Our results showed that miRNA-155 exhibited the lowest expression, while miRNA-222 exhibited the highest expression, followed by miRNA-221. The expression of each individual miRNA was positively correlated with that of the others both pre-RT control and post-RT and inversely correlated with age before RT. Furthermore, RT promoted the overexpression of the selected miRNAs. Their levels were also affected by CVD-linked clinical parameters, treatment and BC side. Modulation of the expression of the selected miRNAs together with other risk factors might be associated with the development of future cardiovascular pathologies. Further confirmatory studies are needed to assess their potential as possible biomarkers in the progression of or as therapeutic targets for RT-induced CVD in BC patients.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers / blood
  • Breast Neoplasms / therapy*
  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / diagnosis*
  • Cardiovascular Diseases / etiology
  • Chemoradiotherapy, Adjuvant / adverse effects
  • Chemoradiotherapy, Adjuvant / methods
  • Disease Progression
  • Dose Fractionation, Radiation
  • Female
  • Gene Expression Profiling
  • Heart / radiation effects
  • Humans
  • Mastectomy
  • MicroRNAs / blood
  • MicroRNAs / metabolism
  • Middle Aged
  • Organs at Risk / radiation effects
  • Radiation Injuries / blood
  • Radiation Injuries / diagnosis*
  • Radiation Injuries / etiology
  • Radiotherapy, Adjuvant / adverse effects
  • Radiotherapy, Adjuvant / methods

Substances

  • Biomarkers
  • MIRN146 microRNA, human
  • MIRN155 microRNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MicroRNAs

Grants and funding

This work was supported by grants from the Instituto de Salud Carlos III (PI 10/02547, PI030786), Centro de Investigación Biomédica en Red en Diabetes y Enfermedades Metabólicas asociadas (CIBER-DEM) and Fondo Europeo de Desarrollo Regional (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.