Integrated transcriptomics and proteomics analysis reveal age-related prognosis and myocardial fibrosis in pediatric DCM

BackgroundDilated cardiomyopathy (DCM) represents the most prevalent form of pediatric cardiomyopathy. However, the characteristics and etiology of this condition across different pediatric age groups remain incompletely elucidated. Methods and resultsData from 88 pediatric patients aged <14 years diagnosed with primary DCM between January 2021 and December 2023 were retrospectively retrieved from the institutional database and analyzed. Patients were stratified into two groups using a 3-year age cutoff. Clinical characteristics, echocardiographic parameters, and biomarkers were documented for each patient to facilitate subsequent analysis. Of these patients, 11 underwent heart transplantation and additional transcriptomic and proteomic analyses were conducted to identify differentially expressed genes (DEGs) and proteins (DEPs). Additionally, cardiac magnetic resonance imaging was utilized to evaluate myocardial fibrosis. Statistically significant disparities were observed between the two age groups with respect to clinical characteristics and clinical outcomes. Patients in the [&le;]3-year-old group exhibited a more favorable prognosis. Multi-omics integrative analysis revealed that genes associated with inflammatory responses and energy metabolism impairment--notably PDK4, CHI3L1, ZBP1 and ANXA1--were enriched in the younger group. In contrast, myocardial inflammation and fibrosis were the predominant features in the older group, as evidenced by the significant upregulation of COL11, CTGF, RO60 and MAT2B. ConclusionsAt both the transcriptomic and translational levels, we uncovered global variations in miRNAs and proteins associated with DCM, following stratification of patients by the 3-year age cutoff. Specifically, energy metabolism dysregulation plays a pivotal role in younger pediatric patients, whereas irreversible myocardial fibrosis may underlie the suboptimal response to conservative therapy in older pediatric patients.