D2.106 - Molecular Clustering Using microRNA Expression Profiles in Pediatric Asthma Reveals Differential Corticosteroid Responsiveness
Background
Asthma is a heterogeneous disease with variable treatment responses. miRNAs play a critical role in asthma pathogenesis and may serve as biomarkers for distinct asthma endotypes. We tried to identify molecular asthma clusters based on miRNA expression profiles in pediatric patients from the Childhood Asthma Management Program (CAMP) cohort.
Method
We performed miRNA profiling and k-means clustering on 492 CAMP participants. Differential miRNA expression and pathway enrichment analyses were conducted, followed by phenotypic and eosinophil-stratified steroid response comparisons.
Results
Three distinct clusters were identified, each with distinct ICS response, unique miRNA expression patterns and enriched biological pathways. Cluster 1 exhibited good inhaled corticosteroid (ICS) responsiveness in participants with peripheral blood eosinophilia (PBE ≥ 300 cells/mm³) but reduced response in those without. Cluster 2 showed poor ICS response regardless of PBE count, while Cluster 3 demonstrated ICS responsiveness independent of eosinophil levels. Cluster 1 exhibited pathways related to KIT signaling, Cluster 2 showed enrichment in cellular senescence pathways, and Cluster 3 had pathways associated with FOXO-mediated transcription.
Conclusion
miRNA profiling revealed distinct asthma endotypes with varied ICS responsiveness based on eosinophil counts.
