Transcriptome signatures of neonatal acute respiratory distress syndrome in a prospective cohort of respiratory distress

BackgroundNeonatal acute respiratory distress syndrome (NARDS) is difficult to differentiate from other respiratory distress conditions in the early stages, and gestational age may affect gene expression. We aimed to identify robust predictive biomarkers for NARDS across varying gestational ages in neonates using whole blood transcriptomics, and investigate the potential underlying pathological mechanisms to provide theoretical insights to the precise treatment of NARDS.MethodsWe conducted a prospective cohort study enrolling neonates presented with respiratory distress. Blood samples were collected upon admission for transcriptomic analysis.ResultsThe pilot cohort included 48 respiratory distress neonates, consisting of 24 diagnosed with NARDS and 24 control subjects diagnosed with respiratory distress syndrome or transient tachypnea of the neonate. Gestational age showed a positive trend on gene expression in peripheral blood. Three key predictive genes for NARDS (ALOX15, PTGDR2, and LIRB3) were identified combined with LASSO, Random Forest (RF), and XGBoost algorithms. Functional enrichment analysis revealed that inflammatory and interferon-related pathways play a significant role in NARDS. These pathways were more suppressed in neonates born before 34 weeks (group LA) than those with larger gestational ages (group MA). Immune cell infiltration analysis indicated the involvement of multiple immune cells in the MA group, while none were detected in the LA group.ConclusionGestational age significantly influences peripheral blood gene expression in neonates with respiratory distress. Interferon-related pathways play a critical role in the pathogenesis of neonatal acute respiratory distress syndrome (NARDS). Furthermore, ALOX15 and PTGDR2 emerge as promising diagnostic biomarkers and potential therapeutic targets for NARDS.