Abstract / Summary
Abstract Background Ulcerative colitis (UC) is an autoimmune inflammatory disease of the digestive tract. While autophagy plays a crucial role in inflammation and immunity, its precise mechanism in UC remains unclear. This study aimed to investigate the molecular characteristics and immune landscape associated with autophagy-related differentially expressed genes (AR-DEGs) in UC. Methods Differentially expressed genes (DEGs) were identified through analysis of the UC dataset (GSE87466), Subsequently, AR-DEGs were identified by intersecting these DEGs with established autophagy-related genes (ARGs) sets. A UC risk diagnostic model was constructed using logistic regression, and its diagnostic value was evaluated via the receiver operating characteristic (ROC) curve analysis. Utilizing AR-DEGs, consensus clustering analysis was performed to stratify UC patients into two distinct subtypes, whose differential characteristics were then thoroughly analyzed and compared. Single-cell sequencing (scRNA-seq) analysis was employed to investigate alterations in cell populations and intercellular communication within UC patients. The expression levels of the identified AR-DEGs were further validated by quantitative real-time PCR (qRT-PCR). Results Our study identified three AR-DEGs: APOL1, CCL2 , and IL-24 . A robust risk diagnostic model was successfully constructed based on these genes, demonstrating strong diagnostic performance (AUC = 0.99). UC patients were successfully stratified into two distinct subtypes. Subtype 1 exhibited heightened immune cell infiltration and significantly elevated expressions of these AR-DEGs. At the single-cell level, these three AR-DEGs mainly showed high expression in endothelial cells and fibroblasts, with concomitant significant alterations in cell proportions and intercellular communication. Validation via qRT-PCR confirmed significantly increased expression of APOL1, CCL2 , and IL-24 in intestinal tissues from UC mouse models and UC patients. Conclusion This study identifies APOL1, CCL2 , and IL-24 as critical autophagy-related biomarkers in the pathogenesis of UC. The diagnostic model constructed based on these genes demonstrates robust clinical predictive value. Furthermore, our findings reveal the significance of these signatures in stratifying UC patients into distinct molecular subtypes with unique immune infiltration patterns and highlight their specific enrichment in endothelial cells and fibroblasts, suggesting a role in remodeling the immune microenvironment via altered intercellular communication. Collectively, these insights not only deepen the understanding of autophagy-mediated immune regulation in UC but also provide potential biomarkers and novel strategies for diagnosis and targeted therapy.