Abstract
BACKGROUND: Doxorubicin, an anthracycline chemotherapy, is routinely utilized for cancer treatment in adolescents and young adults (AYAs) and can lead to cardiac dysfunction at high doses. Anthracycline-induced cardiac impairments are associated with fluctuations in lipid and amino acid metabolism. Identification of unique metabolomic signatures may support the use of metabolomic and lipidomic profiling to identify biomarkers of disease risk and development. These signatures may also reveal pathogenetic links between adiposity and cancer treatment-related cardiac dysfunction. PURPOSE: To identify key metabolites associated with cancer treatment-induced cardiac dysfunction in AYAs with cancer. METHODS: 10 AYAs (M = 5, F = 5) treated with doxorubicin (mean dose = 406.7 ± 124.1 mg/m2) and diagnosed with sarcoma were selected for inclusion in the pilot study analyses, 7 with echocardiogram-defined cardiac pathology and 3 without. Abnormal cardiac function was defined as having left ventricular (LV) ejection fraction ≥ 10-point decrease or having at least two of the following: lateral e’ ≥ 20% drop, septal e’ ≥ 20% drop, or LV global longitudinal strain ≥ 15% drop from baseline to 12 months. Blood samples were collected as a part of routine care prior to doxorubicin chemotherapy (baseline) and at 1 year follow up for quantitative metabolomics profiling via Biocrates MxP Quant 500XL. Two-factor analyses, conducted via MetaboAnalyst, were utilized for metabolite data analysis and comparison. The analyses included diagnosis (cardiac dysfunction vs. normal cardiac function) and time (baseline vs. 12 months post-doxorubicin chemotherapy) on metabolite profiles. RESULTS: The top three positively correlated metabolites with abnormal cardiac function were identified as L-Histidine (r = 0.63, FDR = 0.51), L-Asparagine (r = 0.60, FDR = 0.51), and Deoxycholic acid (r = 0.57, FDR = 0.51). The top three negatively correlated metabolites were 20:5 Cholesterol ester (r = –0.66, FDR = 0.51), 18:3 Cholesterol ester (r = –0.63, FDR = 0.51), and 16:1 Cholesterol ester (r = –0.63, FDR = 0.51). CONCLUSION: Despite non-significant FDR-adjusted p-values, moderate-to-strong correlations and biological clustering of lipid species were observed among our limited sample. These early pilot findings provide preliminary evidence of potential metabolic signatures associated with anthracycline-induced cardiac abnormalities that warrant validation in larger, high-powered cohorts.
Recommended Citation
To, Ethan; Rauschendorfer, Savannah V.; and Wiggs, Michael P.
(2026)
"Potential of Metabolomics as Biomarkers for Cancer Treatment-Induced Cardiac Dysfunction in Adolescents and Young Adults: A Pilot Study,"
International Journal of Exercise Science: Conference Proceedings: Vol. 2:
Iss.
18, Article 85.
Available at:
https://digitalcommons.wku.edu/ijesab/vol2/iss18/85