Abstract
The coexistence of ulcerative colitis (UC) and nonalcoholic steatohepatitis (NASH) involves a intricate interplay, though the precise pathophysiological mechanisms remain elusive. To shed light on this, our study endeavors to unravel the shared gene signatures and molecular mechanisms by employing quantitative bioinformatics analysis on a publicly available RNA-sequencing database. Gene expression profiles of UC (GSE87466) and NASH (GSE89632) were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were analyzed using R software. After identifying common DEGs, functional enrichment analysis, protein-protein interaction (PPI) network analysis and module construction were performed to obtain candidate hub genes. GSE47908 for UC and GSE159676 for NASH were selected to validate the obtained candidate genes. A total of 119 common DEGs were found in NASH and UC patients. Functional and pathway analyses emphasized that viral infection, inflammation and immune response were enriched in these two diseases. After module construction and validation, CD2, CD8A, GNLY, IFI44, NKG7 and OAS2 were identified as hub genes. 6 hub genes and their combined prediction scores were found with an impressive accuracy and sensitivity. Functional estimation, gene set enrichment analysis and immune infiltration signature identification showed notable associations of the six hub genes with T cells, natural killer cells and type I interferon levels. In addition, we constructed UC combined with NASH mice model successfully with significantly higher expression of hub genes in both liver and colonic tissues than those in control group. Our study elucidates 6 hub genes of UC and NASH, which may participate in immune, inflammatory and antiviral effects. These findings provide some potential biochemical markers for further exploration of UC coexistence with NASH.