Genome-wide dna methylation signatures predict the early asymptomatic doxorubicin-induced cardiotoxicity in breast cancer

Michael A. Bauer, Valentina K. Todorova, Annjanette Stone, Weleetka Carter, Matthew D. Plotkin, Ping Ching Hsu, Jeanne Y. Wei, Joseph L. Su, Issam Makhoul

Research output: Contribution to journalArticlepeer-review

Abstract

Chemotherapy with doxorubicin (DOX) may cause unpredictable cardiotoxicity. This study aimed to determine whether the methylation signature of peripheral blood mononuclear cells (PBMCs) prior to and after the first cycle of DOX-based chemotherapy could predict the risk of cardiotoxicity in breast cancer patients. Cardiotoxicity was defined as a decrease in left ventricular ejection fraction (LVEF) by >10%. DNA methylation of PBMCs from 9 patients with abnormal LVEF and 10 patients with normal LVEF were examined using Infinium HumanMethylation450 BeadChip. We have identified 14,883 differentially methylated CpGs at baseline and 18,718 CpGs after the first cycle of chemotherapy, which significantly correlated with LVEF status. Significant differentially methylated regions (DMRs) were found in the promoter and the gene body of SLFN12, IRF6 and RNF39 in patients with abnormal LVEF. The pathway analysis found enrichment for regulation of transcription, mRNA splicing, pathways in cancer and ErbB2/4 signaling. The preliminary results from this study showed that the DNA methylation profile of PBMCs may predict the risk of DOXinduced cardiotoxicity prior to chemotherapy. Further studies with larger cohorts of patients are needed to confirm these findings.

Original languageEnglish (US)
Article number6291
JournalCancers
Volume13
Issue number24
DOIs
StatePublished - Dec 1 2021
Externally publishedYes

Keywords

  • Breast cancer
  • Cardiomyopathy
  • Cardiotoxicity
  • Doxorubicin
  • Methylation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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