Abstract 16961: Evaluation of microRNAs as Novel Markers of Cardiotoxicity in Patients Treated With Anthracycline Therapy for Childhood Cancer
Background: Early detection of anthracycline cardiotoxicity may allow cardioprotective intervention(s) prior to irreversible damage. microRNA (miR) modulation in anthracycline carditoxicity has been identified in animal models, however there are no data regarding circulating miR expression following anthracycline-induced cardiac injury in humans.
Methods: We measured candidate plasma miR expression in thirteen children immediately prior to and six hours following a cycle of anthracycline chemotherapy, and in five control children before and after non-cardiotoxic chemotherapy. Candidate miRs, including miRs-1, -133a, -195, -208a, -29b, -423-5p, and -499a, were selected based on their established roles in regulating stress-induced cardiomyocyte hypertrophy and fibrosis or as circulating biomarkers of cardiac injury. Additionally, miR-146a was selected based on its known upregulation in cardiac tissue following anthracycline-induced cardiac injury.
Results: Children treated with anthracycline had a 2.4-fold increase in plasma miR-208a at 6 hours, compared to controls with a 1.6-fold reduction (p=0.005). Additionally, anthracycline treatment was associated with a 3-fold increase in plasma miR-146a at 6 hours, compared to controls with a 1.5-fold reduction (p=0.028). No differences were seen between groups for other miRs. Of the seven children with > 1.5-fold elevation in miR-208, six (85%) demonstrated evidence of cardiac injury indicated by a reduction in left ventricular shortening fraction or an acute elevation in hs-cTnT (>14pg/mL) post-chemotherapy. Five of the seven (71%) children with > 1.5-fold elevation in miR-146a had evidence of cardiac injury.
Conclusion: Plasma miR-146a and miR-208 are upregulated following anthracycline chemotherapy and may herald acute cardiac injury. Further work is ongoing to evaluate these miRs as early markers of anthracycline-induced cardiotoxicity.
- © 2013 by American Heart Association, Inc.