Circulating microRNA as a biomarker for recovery in pediatric dilated cardiomyopathy

Background: MicroRNAs (miRNAs) are short regulatory RNAs that control gene expression through interacting with the 3'UTR of target messenger RNAs. The purpose of this study was to determine if circulating miRNAs are useful biomarkers of outcome in children with dilated cardiomyopathy (DCM).

Methods: An array for 754 miRNAs and real time polymerase chain reaction confirmation of select miRNAs were performed. Serum from 55 children <18 years old with DCM was analyzed. Samples were drawn from all patients with DCM when undergoing heart transplant evaluation and/or at the time of transplantation. Patients with DCM were categorized based on when their blood was drawn (Pre-Transplant or Transplant) and outcome (Transplant/died or Recovered).

Results: Two miRNAs were significantly up-regulated (hsa-miR-155 and hsa-miR-636) and 2 miRNAs were down-regulated (hsa-miR-646 and hsa-miR-639) in patients with DCM who were transplanted or died compared with patients with DCM who recovered their ventricular function. Receiver operator curves, performed for differences in any 1 of these 4 differentially regulated miRNAs in patients who were transplanted or died compared with patients who recovered, resulted in an area under the receiver operating characteristic curve of 0.875 for the Pre-Transplant blood draw time point and an area under the receiver operating characteristic curve of 0.93 for the day of Transplant time point.

Conclusions: We identified specific miRNAs that are differentially regulated between children with DCM who need a transplant compared with children with DCM who recover. A unique biomarker signature of miRNAs that are specific to children with DCM who have the potential to recover would be valuable in risk stratification of this challenging patient population.