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ORIGINAL RESEARCH article
Front. Cell Dev. Biol.
Sec. Cellular Biochemistry
Volume 13 - 2025 | doi: 10.3389/fcell.2025.1543636
This article is part of the Research Topic Advances in Multi-Omics Technologies in Pathophysiological Processes and Disease Diagnostics View all 3 articles
Metabolomic Profiling and Biomarker Identification for Early Detection and Therapeutic Targeting of Doxorubicin-Induced Cardiotoxicity
Provisionally accepted- 1 Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, Jiangsu Province, China
- 2 Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Background: Doxorubicin (DOX) is a widely used chemotherapeutic agent known for its efficacy against various cancers, but its clinical application is often limited by its cardiotoxic effects. The exact mechanisms of DOX-induced cardiotoxicity remain unclear, requiring further investigation. Early diagnosis is essential to enhance the quality of life and prognosis for patients with malignancies. This study aims to identify biomarkers and therapeutic targets for DOX cardiotoxicity.Methods: Heart tissue samples from 20 DOX-treated cardiotoxic mice and 19 normal controls were analyzed using liquid chromatography-mass spectrometry (LC-MS).Multivariate statistical analysis identified differential metabolites. Key metabolites were assessed using a random forest algorithm, and ROC curves evaluated diagnostic value. H9C2 rat cardiomyoblast cells were cultured to investigate the protective effects of these metabolites.Results: Among 291 metabolites, significant differences emerged between cardiotoxic and normal mice. Five metabolites-4-hydroxy-valeric acid, 2-methylbutanoic acid, traumatic acid, PI(18:2(9Z, 12Z)/0:0), and MIPC(t18:0/24:0(2OH))-showed diagnostic potential. ROC analysis indicated excellent value for 4-hydroxy-valeric acid and PI(18:2(9Z, 12Z)/0:0) and high discriminatory power for 2-methylbutanoic acid (AUC=0. 99). Pathway analysis highlighted glycosylphosphatidylinositol-anchor biosynthesis, unsaturated fatty acids biosynthesis, pantothenate and CoA pathways, among others, associated with DOX-induced cardiotoxicity. In addition, we found that the differential metabolite Cer(d18:0/12:0) can improve DOX-induced myocardial cell damage and inhibit apoptosis-related protein expression at the cellular level. Conclusion: Heart tissue metabolomics with LC-MS identified critical metabolites and pathways associated with DOX cardiotoxicity, suggesting biomarkers for early diagnosis and potential therapeutic targets to mitigate DOX-related cardiotoxicity and improve clinical outcomes.
Keywords: cardiotoxicity, anticancer, Metabolomics, biomarker, Doxorubicin
Received: 11 Dec 2024; Accepted: 31 Mar 2025.
Copyright: © 2025 Ding, Feng, Xu and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Zhongqing Xu, Tongren Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China
Hong Xu, Department of Oncology, First Affiliated Hospital of Soochow University, Suzhou, 215006, Jiangsu Province, China
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.