Bioinformatics Analysis Identifies Apoptosis Gene Biomarkers Linking Psoriasis and Inflammatory Bowel Disease Comorbidity

Abstract

The comorbidity of psoriasis and inflammatory bowel disease (IBD) is well-established, yet the shared molecular mechanisms, particularly the role of apoptosis, remain insufficiently explored. This study aims to identify key apoptosis-related genes that link these two diseases. Microarray data from the GEO database were analyzed. We identified differentially expressed genes (DEGs) using the limma package and constructed co-expression networks via Weighted Gene Co-expression Network Analysis (WGCNA) to find disease-associated modules. Functional enrichment analysis of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways was performed using the clusterProfiler package. Key apoptosis-related genes were refined by applying machine learning algorithms, including Least Absolute Shrinkage and Selection Operator and Random Forest. Immune cell infiltration between diseased and control samples was assessed using single-sample GSEA (ssGSEA). Our integrated analysis identified three central apoptosis-related genes: CCL2, XK, and PRKAR2B. Gene set enrichment analysis indicated their involvement in critical biological processes and signaling pathways. Furthermore, correlation analysis revealed that these genes have strong associations with specific immune cell infiltration patterns, suggesting a potential mechanism linking apoptosis and immune dysregulation in both psoriasis and IBD. This study identifies CCL2, XK, and PRKAR2B as pivotal genes bridging psoriasis and IBD through apoptosis-related mechanisms. These findings shed light on the shared molecular underpinnings of these comorbid conditions and highlight potential targets for future therapeutic strategies.