Recurrence prediction using microRNA expression in hormone receptor positive breast cancer during tamoxifen treatment

Biomarkers. 2018 Dec;23(8):804-811. doi: 10.1080/1354750X.2018.1499131. Epub 2018 Aug 23.

Abstract

Purpose: To identify miRNAs associated with distant recurrence during tamoxifen treatment and build a recurrence prediction model.

Materials and methods: We measured the expression of five miRNAs (miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222). A total of 176 tumour tissues from 176 patients who had hormone receptor positive breast cancer with tamoxifen treatment were used to measure miRNA expression using quantitative real-time PCR (qRT-PCR).

Results: The five miRNAs were all up-regulated in distant recurrence cases within 5 years after surgery and during tamoxifen treatment. Kaplan-Meier survival analyses based on expression cut-offs determined by receiver characteristics curves (ROC) showed that high expression of miR-134, miR-125b-5P, miRNA-30a, miR-10a-5p and miR-222 were significantly (log-rank p-value =0.006, p-value <0.0001, p-value <0.0001, p-value <0.0001 and p-value <0.0001, respectively) associated with short relapse-free time. Our results were used to build a combined 3 miRNAs expression model. It could be used to categorize high-risk subset of patients with short relapse-free survival (AUC =0.891, p-value <0.0001).

Conclusions: Distant recurrence during tamoxifen treatment of hormone positive breast cancer might be affected by tamoxifen resistance related miRNAs. Such distant recurrence can be predicted using miRNA measurement.

Keywords: Breast cancer; microRNA; molecular markers; prognostic factors.

MeSH terms

  • Aged
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • MicroRNAs / analysis*
  • MicroRNAs / genetics
  • Middle Aged
  • Neoplasm Recurrence, Local / diagnosis*
  • Neoplasm Recurrence, Local / mortality
  • Postoperative Period
  • Predictive Value of Tests
  • Prognosis
  • Survival Analysis
  • Tamoxifen / therapeutic use*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • MicroRNAs
  • Tamoxifen