Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core Genes in Ulcerative Colitis

Abstract

Background Ulcerative colitis is a recurrent autoimmune disease. At present, the pathogenesis of UC is not completely clear. Hence, the etiology and underlying molecular mechanism need to be further investigated. Methods Three sets of microarray datasets were included from the Gene Expression Omnibus database. The differentially expressed genes in two sets of datasets were analyzed using the R software, and the core genes of UC were screened using machine learning. The sensitivity and specificity of the core genes were evaluated with the receiver operating characteristic curve in another microarray dataset. Subsequently, the CIBERSORT tool was used to analyze the relationship between UC and its core genes and immune cell infiltration. To verify the relationship between UC and core genes and the relationship between core genes and immune cell infiltration in vivo. Results A total of 36 DEGs were identified. AQP8, HMGCS2 , and VNN1 were determined to be the core genes of UC. These genes had high sensitivity and specificity in receiver operating characteristic curve analysis. According to the analysis of immune cell infiltration, neutrophils, monocytes, and macrophages were positively correlated with UC. AQP8, HMGCS2 , and VNN1 were also correlated with immune cell infiltration to varying degrees. In vivo experiments verified that the expressions of neutrophils, monocytes, and macrophages increased in the UC colon. Furthermore, the expressions of AQP8 and HMGCS2 decreased, whereas that of VNN1 increased. Azathioprine treatment improved all the indicators to different degrees. Conclusion AQP8, HMGCS2 , and VNN1 are the core genes of UC and exhibit different degrees of correlation with immune cells. These genes are expected to become new therapeutic targets for UC. Moreover, the occurrence and development of UC are influenced by immune cell infiltration.

The HMGCS2-associated hub genes as promising targets for ulcerative colitis patients

“…In a study of colon cancer, it was found that inhibition of HMGCS2 increased glycolysis and decreased fatty acid βoxidation in colon cancer cells (Kim et al, 2023). In a previous integrated bioinformatics analysis study, HMGCS2 was found to be a relevant gene in the development of UC, which may be associated with the in ltration of neutrophils, monocytes and macrophages (Li et al, 2022;Zhao et al, 2023). Compared with normal tissues, HMGCS2 expression level was inhibited in the intestinal epithelium of UC patients in active phase (Kim et al, 2021), but its role in remission phase has not been studied.…”