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Molecular Biology

, Volume 53, Issue 3, pp 371–378 | Cite as

A Group of Hypermethylated miRNA Genes in Breast Cancer and Their Diagnostic Potential

  • E. A. Filippova
  • V. I. Loginov
  • I. V. Pronina
  • D. S. Khodyrev
  • A. M. Burdennyy
  • T. P. Kazubskaya
  • E. A. BragaEmail author
GENOMICS. TRANSCRIPTOMICS
  • 13 Downloads

Abstract

miRNA genes play an important role in cancer pathogenesis, while they may be suppressed by hypermethylation. Here, we assess the diagnostic potential of a group of hypermethylated miRNA genes (MIR-124-1, MIR-124-3, MIR-125B-1, MIR-127, MIR-132, MIR-193a, and MIR-34b/c) in a representative set of 70 breast cancer samples and 17 breast tissue samples from deceased donors with no malignancies. For these seven genes, the methylation status is determined using the methylation-specific PCR. Methylation reached 26–76% in tumor specimens, 1‒27% in paired considered normal breast tissues, and 0–18% in breast tissue from deceased donors. By quantitative RT-PCR, reduced expression levels of the investigated miRNAs are detected, with a negative correlation of expression levels with gene hypermethylation. Combinations of three or four hypermethylation biomarkers, namely, MIR-124-1, MIR-125B-1, MIR-127, and MIR-34b/c are found suitable for breast cancer diagnostics; with sensitivity (76‒93%), specificity (88‒100%), and AUC (0.88‒0.94). Notably, the MIR-127 gene was hypermethylated only in the tumor samples of patients with metastases, and, therefore, should be tested as a marker of breast cancer dissemination. These findings may lead to improvement in the management of breast cancer.

Keywords:

breast cancer miRNA genes hypermethylation diagnostic markers metastasis marker MIR-127 

Notes

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Copyright information

© Pleiades Publishing, Inc. 2019

Authors and Affiliations

  • E. A. Filippova
    • 1
  • V. I. Loginov
    • 1
    • 2
  • I. V. Pronina
    • 1
  • D. S. Khodyrev
    • 3
  • A. M. Burdennyy
    • 1
  • T. P. Kazubskaya
    • 4
  • E. A. Braga
    • 1
    • 2
    Email author
  1. 1.Institute of General Pathology and PathophysiologyMoscowRussia
  2. 2.Research Center of Medical GeneticsMoscowRussia
  3. 3.Federal Research Clinical Center of Specialized Types of Medical Care and Medical Technologies, Federal Medico-Biological Agency of RussiaMoscowRussia
  4. 4.Blokhin National Medical Research Center of Oncology, Ministry of Health of the Russian FederationMoscowRussia

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