Identification of differential gene expression related to epirubicin-induced cardiomyopathy in breast cancer patients.

BACKGROUND

Epirubicin is a potent chemotherapeutic agent for the treatment of breast cancer. However, it may lead to cardiotoxicity and cardiomyopathy, and no reliable biomarker was available for the early prediction of epirubicin-induced cardiomyopathy.

METHODS

Global gene expression changes of peripheral blood cells were studied using high-throughput RNA sequencing in three pair-matched breast cancer patients (patients who developed symptomatic cardiomyopathy paired with patients who did not) before and after the full session of epirubicin-based chemotherapy. Functional analysis was conducted using gene ontology and pathway enrichment analysis.

RESULTS

We identified 13 significantly differentially expressed genes between patients who developed symptomatic epirubicin-induced cardiomyopathy and their paired control who did not. Among them, the upregulated Bcl-associated X protein was related to "apoptosis," while the downregulated 5'-aminolevulinate synthase 2 (ALAS2) was related to both "glycine, serine, and threonine metabolism" and "porphyrin and chlorophyll metabolism" in pathway enrichment analysis.

CONCLUSIONS

ALAS2 and the metabolic pathways which were involved may play an important role in the development of epirubicin-induced cardiomyopathy. ALAS2 may be useful as an early biomarker for epirubicin-induced cardiotoxicity detection.