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

Po-Yen Hsu; Wan-Hong Huang; Yi-Yun Lee; Robert Passier; Szu-Chin Li; Chong-Lin Hong; Shih-Kai Hung; Hong-Yi Lin; Chun-Hung Lin; Chen-Yu Chien; Yi-Da Li; Hsiang-Chun Lee; Laurent Désaubry; Canan G. Nebigil; Michael W.Y. Chan

doi:10.1016/j.jacbts.2026.101510

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

Po-Yen Hsu
, Wan-Hong Huang
, Yi-Yun Lee
, Robert Passier
, Szu-Chin Li
, Chong-Lin Hong
, Shih-Kai Hung
, Hong-Yi Lin
, Chun-Hung Lin
, Chen-Yu Chien
, Yi-Da Li
, Hsiang-Chun Lee
, Laurent Désaubry
, Canan G. Nebigil^*
, Michael W.Y. Chan^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

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. m PIH1D1 may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.

Original language	English
Article number	101510
Number of pages	14
Journal	JACC: Basic to Translational Science
Volume	11
Issue number	4
Early online date	11 Mar 2026
DOIs	https://doi.org/10.1016/j.jacbts.2026.101510
Publication status	Published - Apr 2026

Keywords

breast cancer
cardiotoxicity
DNA methylation
doxorubicin
PIH1D1

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Hsu, P.-Y., Huang, W.-H., Lee, Y.-Y., Passier, R., Li, S.-C., Hong, C.-L., Hung, S.-K., Lin, H.-Y., Lin, C.-H., Chien, C.-Y., Li, Y.-D., Lee, H.-C., Désaubry, L., Nebigil, C. G., & Chan, M. W. Y. (2026). Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients. JACC: Basic to Translational Science, 11(4), Article 101510. https://doi.org/10.1016/j.jacbts.2026.101510

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

abstract = "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. m PIH1D1 may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.",

keywords = "breast cancer, cardiotoxicity, DNA methylation, doxorubicin, PIH1D1",

author = "Po-Yen Hsu and Wan-Hong Huang and Yi-Yun Lee and Robert Passier and Szu-Chin Li and Chong-Lin Hong and Shih-Kai Hung and Hong-Yi Lin and Chun-Hung Lin and Chen-Yu Chien and Yi-Da Li and Hsiang-Chun Lee and Laurent D{\'e}saubry and Nebigil, \{Canan G.\} and Chan, \{Michael W.Y.\}",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors.",

year = "2026",

month = apr,

doi = "10.1016/j.jacbts.2026.101510",

language = "English",

volume = "11",

journal = "JACC: Basic to Translational Science",

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Hsu, P-Y, Huang, W-H, Lee, Y-Y, Passier, R, Li, S-C, Hong, C-L, Hung, S-K, Lin, H-Y, Lin, C-H, Chien, C-Y, Li, Y-D, Lee, H-C, Désaubry, L, Nebigil, CG & Chan, MWY 2026, 'Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients', JACC: Basic to Translational Science, vol. 11, no. 4, 101510. https://doi.org/10.1016/j.jacbts.2026.101510

TY - JOUR

T1 - Methylated PIH1D1 as a Heart-Specific Biomarker for Anthracycline-Induced Cardiac Remodeling in Breast Cancer Patients

AU - Hsu, Po-Yen

AU - Huang, Wan-Hong

AU - Lee, Yi-Yun

AU - Passier, Robert

AU - Li, Szu-Chin

AU - Hong, Chong-Lin

AU - Hung, Shih-Kai

AU - Lin, Hong-Yi

AU - Lin, Chun-Hung

AU - Chien, Chen-Yu

AU - Li, Yi-Da

AU - Lee, Hsiang-Chun

AU - Désaubry, Laurent

AU - Nebigil, Canan G.

AU - Chan, Michael W.Y.

PY - 2026/4

Y1 - 2026/4

N2 - 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. m PIH1D1 may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.

AB - 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. m PIH1D1 may complement troponin-I in risk assessment and cardiotoxicity management for patients undergoing anthracycline-based chemotherapy.

KW - breast cancer

KW - cardiotoxicity

KW - DNA methylation

KW - doxorubicin

KW - PIH1D1

UR - https://www.scopus.com/pages/publications/105032237855

U2 - 10.1016/j.jacbts.2026.101510

DO - 10.1016/j.jacbts.2026.101510

M3 - Article

AN - SCOPUS:105032237855

SN - 2452-302X

VL - 11

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 4

M1 - 101510

ER -

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

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