Circulating serum microRNA-345 correlates with unfavorable pathological response to preoperative chemoradiotherapy in locally advanced rectal cancer

Oncotarget. 2016 Sep 27;7(39):64233-64243. doi: 10.18632/oncotarget.11649.

Abstract

Preoperative chemoradiotherapy (pre-CRT) has been represented as the standard treatment for locally advanced rectal cancer (LARC), but large variations of tumor radiation response to CRT have been reported in the clinic. To explore the function of microRNAs as potential therapeutic predictors of pre-CRT pathological response in LARC, we analyzed global miRNA expression in CRT-sensitive and CRT-resistant groups before treatment. MiR-345 was significantly elevated in the CRT-resistant group. Therefore, miR-345 was selected as a candidate for further analysis. We assessed the correlation between the miRNA signatures and the chemoradiotherapeutic response in 20 randomly selected LARC tissue samples (Validation set) and 87 serum samples (Training set) by qRT-PCR. Further, we validated the results in 42 randomly selected LARC serum samples (Validation set). High miR-345 expression was significantly correlated with unfavorable pre-CRT pathological response in tissue and serum. Moreover, low miR-345 levels predicted superior 3-year local recurrence free survival (LRFS). Taken together, circulating serum miR-345 correlates with unfavorable pre-CRT response and poor locoregional control in LARC. It might be a promising biomarker to facilitate patient stratification for personalized treatment.

Keywords: personalized treatment; preoperative chemoradiotherapy; rectal cancer; serum mirna.

Publication types

  • Validation Study

MeSH terms

  • Adenocarcinoma / blood
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma / therapy*
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / blood
  • Biomarkers, Tumor / genetics*
  • Chemoradiotherapy, Adjuvant*
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics*
  • Disease-Free Survival
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Profiling
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics*
  • Middle Aged
  • Neoadjuvant Therapy*
  • Neoplasm Recurrence, Local
  • Patient Selection
  • Precision Medicine
  • Predictive Value of Tests
  • Radiation Tolerance / genetics
  • Rectal Neoplasms / blood
  • Rectal Neoplasms / genetics*
  • Rectal Neoplasms / pathology
  • Rectal Neoplasms / therapy*
  • Reproducibility of Results
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • Biomarkers, Tumor
  • Circulating MicroRNA
  • MIRN345 microRNA, human
  • MicroRNAs