Integrated bioinformatics analysis identifies Itgam and Itgb2 as immune-related hub genes in arrhythmogenic right ventricular cardiomyopathy

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited myocardial disease characterized by ventricular arrhythmias, fibrofatty myocardial replacement, heart failure, and sudden cardiac death. Although genetic abnormalities are central to ARVC, the downstream molecular mechanisms, particularly immune-inflammatory changes, remain incompletely understood. This study aimed to identify key genes and pathways associated with ARVC-related cardiac remodeling using integrated bioinformatics analysis. Methods Two ARVC-related cardiac transcriptomic datasets, GSE101301 and GSE181868, were obtained from the Gene Expression Omnibus database. After dataset integration and batch-effect correction, differentially expressed genes (DEGs) were identified using the limma package. Principal component analysis (PCA), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA), and protein–protein interaction (PPI) network analysis were performed to characterize disease-related molecular features. Hub genes were screened using Cytoscape-based topological algorithms, and their disease associations were explored using the Comparative Toxicogenomics Database (CTD). Results A total of 190 DEGs were identified between ARVC-related disease samples and control samples. PCA showed clear separation between the two groups. Functional enrichment analysis indicated that these DEGs were mainly involved in inflammatory response, innate immune response, neutrophil chemotaxis, extracellular matrix-related functions, chemokine signaling, PI3K-Akt signaling, Toll-like receptor signaling, and NF-κB signaling. WGCNA identified three major gene co-expression modules. Through PPI network analysis and integrated hub gene screening, four hub genes were identified: Cd68, Itgam, Itgb2, and Tyrobp. Among them, Itgam and Itgb2 were consistently highlighted by both PPI and Metascape analyses. Heatmap analysis showed that all four hub genes were upregulated in disease samples compared with controls. CTD analysis further suggested their potential associations with heart disease, right ventricular hypertrophy, heart failure, cardiovascular disease, and inflammation. Conclusions This study identified Itgam and Itgb2 as potential immune-related hub genes in ARVC-related cardiac transcriptomic profiles. These findings suggest that immune-inflammatory remodeling may contribute to ARVC-associated myocardial remodeling and provide candidate molecular markers for future mechanistic and translational studies.