Association between miR-21/146a/155 level changes and acute genitourinary radiotoxicity in prostate cancer patients: A pilot study

Pathol Res Pract. 2019 Apr;215(4):626-631. doi: 10.1016/j.prp.2018.12.007. Epub 2018 Dec 10.

Abstract

Introduction: Nearly sixty percent of patients with prostate cancer (PCa) undergo radiation therapy (RT). During the course of treatment patients may experience normal tissue reactions. It is a well established fact that genetic and epigenetic mechanisms, such as microRNA (miRNA) level changes might be associated with radiotoxicity, as a response to irradiation.

Materials and methods: This is the first study that has investigated levels of radiosensory miRNAs in association with acute genitourinary radiotoxicity extracted from peripheral blood mononuclear cells (PBCs), in three points; before RT (BRT), after RT (ART) and on the first control examination (FCONT). We measured levels of miR-21/146a/155 expression by quantitative real-time PCR (qRT-PCR), comparative ΔΔCt method, in fifteen patients with localized prostate cancer, treated with three-dimensional conformal radiotherapy (3DCRT). Nine subjects have experienced acute genitourinary (GU) radiotoxicity whereas six where without GU radiotoxicity.

Results: Firstly, we detected the highest levels of miR-21 in ART group (p = 0.043) in the patients with acute GU radiotoxicity. Secondly, we found trend towards higher miR-21 levels and significantly higher levels of miR-146a/155 within the patients with acute GU toxicity than in patients without (p = 0.068, p = 0.016, and p = 0.010, respectively). Thirdly, we detected significant change in miR-146a/155 levels within the patients without acute GU radiotoxicity during RT p = 0.042, and p = 0.041, respectively).

Conclusion: miR-21/146a/155 might be useful potential factors of radiosensitivity and acute genitourinary radiotoxicity in prostate cancer patients. miRNA might have great potential as predictors of various pathological conditions extracted from PBMCs.

Keywords: Acute genitourinary radiotoxicity; Conformal radiotherapy; Prostate cancer; miR-146a; miR-155; miR-21.

MeSH terms

  • Aged
  • Humans
  • Male
  • MicroRNAs / blood*
  • Middle Aged
  • Pilot Projects
  • Prostatic Neoplasms / blood
  • Prostatic Neoplasms / radiotherapy*
  • Radiotherapy, Conformal / adverse effects*
  • Urinary Bladder / radiation effects*

Substances

  • MIRN146 microRNA, human
  • MIRN155 microRNA, human
  • MIRN21 microRNA, human
  • MicroRNAs