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

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 Omni...

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Detalles Bibliográficos
Autores principales: Zhao, Danya, Qin, Danping, Yin, Liming, Yang, Qiang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296601/
https://www.ncbi.nlm.nih.gov/pubmed/37383675
http://dx.doi.org/10.2147/PGPM.S406644
Descripción
Sumario: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.