Identification of ferroptosis-related genes in pediatric Crohn’s disease using bioinformatics approaches

Ferroptosis is increasingly implicated as a critical pathogenic mechanism in inflammatory bowel disease (IBD). This study employed integrated bioinformatics approaches to identify key ferroptosis-related genes (FRGs), dysregulated signaling pathways, and immune infiltration patterns in pediatric Crohn's disease (PCD). Gene expression profiles from the GSE117993 dataset (92 PCD patients, 55 healthy controls) were analyzed to identify differentially expressed genes (DEGs). FRGs were curated from the FerrDb database. Intersection analysis revealed FRGs-DEGs, which underwent functional enrichment analysis. Protein-protein interaction (PPI) network analysis using CytoHubba identified hub genes. Immune cell infiltration was assessed via single-sample gene set enrichment analysis (ssGSEA). The diagnostic potential of hub genes was evaluated using receiver operating characteristic (ROC) curve analysis in two independent validation cohorts (GSE126124, GSE62207). Bioinformatics analysis identified 1,074 DEGs, including 21 FRGs-DEGs. Enrichment analysis implicated these FRGs-DEGs in metabolic regulation and IL-17 signaling pathway. PPI analysis identified five hub genes: PTGS2, IFNG, IL1B, IDO1, and NOS2. ssGSEA revealed significant accumulation of myeloid-derived suppressor cells (MDSCs) and neutrophils in PCD. Validation results confirmed that all hub genes were significantly differentially expressed (p < 0.01), with IL1B exhibiting the best diagnostic performance. This study reveals promising molecular targets and mechanistic insights to advance PCD diagnosis and precision therapy.