Identification of pyroptosis-related hub genes and immune cell infiltration in IgA nephropathy via bioinformatics analysis.

This study aimed to identify pyroptosis-related hub genes and investigate immune cell infiltration in IgA nephropathy (IgAN) using bioinformatics and experimental validation. Gene expression data from the GEO database (GSE93798) were analyzed, and differential expression analysis was performed using the limma R package. LASSO regression and SVM algorithms were employed to select feature genes. A total of 19 pyroptosis-related differentially expressed genes (nine up-regulated and 10 down-regulated) were identified, with six hub genes (BHLHE40, JUN, CEBPB, ACE2, IL1B, and CD14) showing high diagnostic accuracy for discriminating IgAN from normal samples (AUC > 0.9). Gene Ontology (GO) and KEGG analyses revealed involvement in immune response, cell migration, and inflammation-related signaling pathways. Immune cell infiltration analysis showed higher levels of CD8+ T cells, macrophages, and neutrophils in IgAN. Validation using GSE99339 confirmed these findings, with the hub genes also demonstrating high AUC values in this independent dataset. The differential expression of these genes was validated in both human kidney tissues and serum samples. This study provides potential biomarkers and therapeutic targets for IgAN by elucidating pyroptosis-related genes and immune cell infiltration profiles.