Investigation of Potential Genetic Biomarkers and Molecular Mechanism of Ulcerative Colitis Utilizing Bioinformatics Analysis

Abstract

Objectives. To reveal the molecular mechanisms of ulcerative colitis (UC) and provide potential biomarkers for UC gene therapy. Methods. We downloaded the GSE87473 microarray dataset from the Gene Expression Omnibus (GEO) and identified the differentially expressed genes (DEGs) between UC samples and normal samples. Then, a module partition analysis was performed based on a weighted gene coexpression network analysis (WGCNA), followed by pathway and functional enrichment analyses. Furthermore, we investigated the hub genes. At last, data validation was performed to ensure the reliability of the hub genes. Results. Between the UC group and normal group, 988 DEGs were investigated. The DEGs were clustered into 5 modules using WGCNA. These DEGs were mainly enriched in functions such as the immune response, the inflammatory response, and chemotaxis, and they were mainly enriched in KEGG pathways such as the cytokine-cytokine receptor interaction, chemokine signaling pathway, and complement and coagulation cascades. The hub genes, including dual oxidase maturation factor 2 (DUOXA2), serum amyloid A (SAA) 1 and SAA2, TNFAIP3-interacting protein 3 (TNIP3), C-X-C motif chemokine (CXCL1), solute carrier family 6 member 14 (SLC6A14), and complement decay-accelerating factor (CD antigen CD55), were revealed as potential tissue biomarkers for UC diagnosis or treatment. Conclusions. This study provides supportive evidence that DUOXA2, A-SAA, TNIP3, CXCL1, SLC6A14, and CD55 might be used as potential biomarkers for tissue biopsy of UC, especially SLC6A14 and DUOXA2, which may be new targets for UC gene therapy. Moreover, the DUOX2/DUOXA2 and CXCL1/CXCR2 pathways might play an important role in the progression of UC through the chemokine signaling pathway and inflammatory response.