Metabolomic profiling identified key metabolites, such as sebacate and 2-hydroxyhippurate, as candidate predictors of doxorubicin-induced cardiotoxicity in breast cancer patients, achieving an AUC of 0.855.
Cohort (n=27)
No
Can untargeted metabolomic profiling identify early biomarkers of doxorubicin-induced cardiotoxicity in breast cancer patients?
Metabolomic profiling identified candidate plasma biomarkers that may help predict early doxorubicin-induced cardiotoxicity in breast cancer patients, potentially enabling timely interventions.
Abstract Background Doxorubicin (DOX)-based chemotherapy has improved survival outcomes in breast cancer patients but is often limited by doxorubicin-induced cardiotoxicity (DIC). Currently, no validated biomarkers can predict early DIC. Identifying novel biomarkers is essential for detecting patients at higher risk and enable timely interventions before irreversible cardiac injury occurs. Methods Twenty-seven breast cancer patients treated with DOX-containing chemotherapy were stratified by change in left ventricular ejection fraction (LVEF): 19 patients who maintained normal cardiac function (normal, decline 10%). Plasma samples were collected at baseline and after chemotherapy for untargeted metabolomic profiling. Both baseline and pre–post designs were employed to capture static and dynamic metabolic alterations associated with DIC. Stepwise logistic regression was used to filter non-informative metabolites, and predictive performance was further validated using Random Forest modeling. Results A well-marked separation of plasma metabolomic profiles was observed between normal and abnormal cardiotoxicity groups at baseline (T0). Statistical analysis identified 100 significant metabolites at baseline (T0) and 78 metabolites after the first cycle of chemotherapy (T0-T1), with 10 metabolites common to both time-points: 3-phosphoglycerate, 2-hydroxyphenylacetate, inosine, taurine, suberate (C8-DC), sebacate (C10-DC), sphingadienine, oxindolylalanine. Machine learning models identified key metabolites (e.g., sebacate C10-DC, 2-hydroxyhippurate, orotate, picolinate, and suberate C8-DC) as candidate predictors of cardiotoxicity, achieving moderate discriminatory performance in cross-validation, with higher specificity than sensitivity, indicating limited detection of abnormal cases. Conclusions Metabolomic profiling shows potential for early detection of DIC in breast cancer patients, supporting personalized interventions to prevent irreversible cardiac damage.
Singh et al. (Sat,) conducted a cohort in Breast cancer (n=27). Doxorubicin-containing chemotherapy vs. Patients maintaining normal cardiac function was evaluated. Metabolomic profiling identified key metabolites, such as sebacate and 2-hydroxyhippurate, as candidate predictors of doxorubicin-induced cardiotoxicity in breast cancer patients, achieving an AUC of 0.855.