Senescence-related gene signatures in Crohn’s disease: integrating bulk and single-cell RNA sequencing analysis

Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease (IBD). Recent studies have revealed that intestinal tissues of CD patients exhibit progeroid-like features, suggesting that cellular senescence may contribute to CD progression. However, the specific roles of senescence-related genes in CD and their impact on prognosis remain unclear. This study identified CD-associated senescence genes through differential expression analysis. Machine learning algorithms were employed to further screen for hub genes. Gene Set Enrichment Analysis (GSEA) was performed to explore the potential functions of these hub genes, and their association with immune cell infiltration was assessed using the CIBERSORT algorithm. Independent external datasets were utilized to validate the diagnostic model's robustness, with additional validation of hub gene expression through mouse models and clinical samples. Furthermore, single-cell RNA sequencing (scRNA-seq) data analysis was conducted to examine senescence heterogeneity at the single-cell level in CD patients. This study identified five senescence-associated hub genes (STAT1, S100A11, FILIP1L, F3, and HPS5) significantly correlated with CD. GSEA revealed that these genes were closely associated with tissue inflammatory responses, nutrient absorption, and energy metabolism. Immune infiltration analysis further demonstrated a strong correlation between the expression levels of these five genes and the degree of immune cell infiltration. scRNA-seq analysis indicated significant differences in senescence levels between affected and unaffected areas in CD patients. Senescence-related genes are closely associated with disease progression in CD patients.