Integrated Bioinformatics Analysis and Experimental Verification of Immune Cell Infiltration and the Related Core...

Area of Science:

• Genomics and Bioinformatics
• Immunology
• Gastroenterology

Background:

• Ulcerative colitis (UC) is a recurrent autoimmune disease with unclear pathogenesis.
• Further investigation into the etiology and molecular mechanisms of UC is crucial.

Purpose of the Study:

• To identify core genes associated with ulcerative colitis (UC) using bioinformatics.
• To investigate the relationship between identified core genes and immune cell infiltration in UC.
• To explore the potential of these core genes as therapeutic targets for UC.

Main Methods:

• Analysis of three Gene Expression Omnibus microarray datasets.
• Identification of differentially expressed genes (DEGs) and screening of core UC genes using machine learning.
• Evaluation of core gene diagnostic value via receiver operating characteristic (ROC) curve analysis.
• Assessment of immune cell infiltration and its correlation with UC and core genes using CIBERSORT.
• In vivo validation of gene and immune cell expression in UC colon tissue.

Main Results:

• Thirty-six differentially expressed genes (DEGs) were identified, with AQP8, HMGCS2, and VNN1 identified as core UC genes.
• These core genes demonstrated high sensitivity and specificity in ROC analysis.
• Neutrophils, monocytes, and macrophages were positively correlated with UC and showed varying correlations with the core genes.
• In vivo studies confirmed increased immune cell infiltration in UC colons, with decreased AQP8/HMGCS2 and increased VNN1 expression.
• Azathioprine treatment showed a positive impact on these indicators.

Conclusions:

• AQP8, HMGCS2, and VNN1 are identified as core genes in UC, correlating with immune cell infiltration.
• These genes represent potential novel therapeutic targets for ulcerative colitis.
• Immune cell infiltration plays a significant role in the development and progression of UC.