Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients

Anthracyclines, key chemotherapy agents, pose cardiotoxicity risks. In a 3-year study of 89 breast cancer patients treated with doxorubicin or epirubicin, more than 50% showed reduced left ventricular ejection fraction and progressive ventricular dilation. Although troponin-I flagged acute damage, it failed to predict long-term remodeling. Using a human methylome atlas, researchers identified 33 heart-specific methylated CpG sites and validated methylated PIH1D1 (mPIH1D1) as a novel biomarker. Elevated mPIH1D1 levels strongly correlated with ventricular dilation but not left ventricular ejection fraction decline, indicating its sensitivity to early cardiac remodeling. mPIH1D1 may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.