Circulating microRNAs: Potential Markers of Cardiotoxicity in Children and Young Adults Treated With Anthracycline Chemotherapy

Background Biomarkers for early detection of anthracycline (AC)‐induced cardiotoxicity may allow cardioprotective intervention before irreversible damage. Circulating micro RNA s (mi RNAs ) are promising biomarkers of cardiovascular disease, however, have not been studied in the setting of AC‐induced cardiotoxicity. This study aimed to identify AC‐induced alterations in plasma mi RNA expression in children and correlate expression with markers of cardiac injury. Methods and Results Candidate plasma profiling of 24 mi RNA s was performed in 33 children before and after a cycle of AC (n=24) or noncardiotoxic chemotherapy (n=9). Relative mi RNA changes between the pre‐ and postcycle time points (6, 12, and 24 hours) were determined within each treatment group and compared across groups. Plasma mi RNA expression patterns were further explored with respect to AC dose and high‐sensitivity troponin T. Greater chemotherapy‐induced dysregulation was observed in this panel of candidate, cardiac‐related plasma mi RNA s in patients receiving anthracyclines compared with those receiving noncardiotoxic chemotherapy (24‐hour MANOVA ; P =0.024). Specifically, plasma miRs‐29b and ‐499 were upregulated 6 to 24 hours post‐AC, and their postchemotherapy expression significantly correlated with AC dose. Patients with acute cardiomyocyte injury (high‐sensitivity troponin T increase ≥5 ng/L from baseline) demonstrated higher expression of miR‐29b and miR‐499 post‐AC compared with those without. Conclusions In this pilot study, cardiac‐related plasma mi RNA s are dysregulated following ACs. Plasma miR‐29b and ‐499 are acutely elevated post‐AC, with dose response relationships observed with anthracycline dose and markers of cardiac injury. Further evaluation of mi RNA s may provide mechanistic insight into AC‐induced cardiotoxicity and yield biomarkers to facilitate earlier intervention to mitigate cardiotoxicity.