Identification and validation of PANoptosis and autophagy-related molecular characterization in ulcerative colitis

Abstract

Abstract Ulcerative colitis (UC) is a chronic, relapsing inflammatory disorder of the gastrointestinal tract. Programmed cell death (PCD), such as PANoptosis and autophagy, is involved in various inflammation- and immune-related diseases. This study aimed to examine the molecular signature and the associated immune cell infiltration of the PANoptosis- and autophagy-related differentially expressed genes (DEGs) in UC. Ten PANoptosis-related hub DEGs, including PDGFRB, TIMP1, MMP2, CD44, TIMP2, TGFB2, IL6, TIMP3, IL1B, HGF, and four autophagy-related hub DEGs, including CCL2, TGFB1, PPARG, and CXCR4, were identified. These hub genes were associated with cell chemotaxis, wound healing and positive regulation of MAPK cascade. Immune infiltration analysis revealed UC patients exhibited a higher infiltration of immunocytes and these hub genes were closely related to a various of immune cell infiltrations. Through the machine learning algorithms, five key candidate genes, TIMP1, TIMP2, TIMP3, IL6, and CCL2, showed a good diagnostic performance in distinguishing UC patients from healthy individuals. Furthermore, these five key candidate genes were highly expressed in inflammatory fibroblasts (IAFs) by single-cell sequencing analysis. The expression levels of the key candidate genes exhibited significant differences in the colon mucosa of UC patients. Our findings indicated that PANoptosis and autophagy or crosstalk between them might be implicated in immune dysregulation and wound healing in UC via regulating specific immune cells or IAFs and interacting with key signals such as cell chemotaxis and MAPK signaling pathways.