Identification of Critical Modules and Biomarkers of Ulcerative Colitis by Using WGCNA

Yifan Yuan,1,2,* Na Li,1,2,* Mingyue Fu,1,2,* Mei Ye1,2 1Department of Gastroenterology, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China; 2Hubei Clinical Centre and Key Laboratory of Intestinal and Colorectal Diseases, Zhongnan Hospital, Wuhan University, Wuhan, Hubei, 430071, China*These authors contributed equally to this workCorrespondence: Mei Ye, Email wumeiye08@163.comBackground: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon and rectum that has no exact cause and is characterized by relapsing and remitting episodes. We aimed to find biomarkers of UC and its causes.Methods: We got GSE73661 from the GEO database and used WGCNA to find DEGs that were expressed in the same way in both normal and UC samples. To identify the co-expression modules, we used Weighted Gene Co-Expression Network Analysis. Next, we selected genes that were both DEGs and parts of main modules. Later, three datasets were used to find the hub genes, and qRT-PCR was utilized to confirm the in-silico findings. Additionally, we analyzed the connection between the hub genes and the filtration of immune cells in UC. Using the databases, we made predictions about the miRNAs and lncRNAs that regulate the hub genes and predicted possible therapeutic drugs.Results: We found 822 DEGs and three main modules related to immunity, endoplasmic reticulum, and metabolism. Using another three datasets and human samples to confirm the mRNA expression of these genes in UC patients, XBP1 and PLPP1 were selected as hub genes, and had excellent diagnostic potential. According to the findings of the immune infiltration, patients with UC exhibited a larger proportion of immune cells. And hub genes, particularly XBP1, were closely linked to a number of immune cell infiltrations. Based on the databases and hub genes, a lncRNA-miRNA-mRNA network, including two miRNAs (miR-214-3p and miR-93-5p), two hub genes, and 124 lncRNAs, and potential therapeutic medicine were identified.Conclusion: We found two new genes, XBP1 and PLPP1, that are involved in UC and can help diagnose and measure the disease. XBP1 also relates to clinical scores and immune cells. We suggested a gene network and possible drugs based on them.Keywords: ulcerative colitis, hub genes, biomarkers, bioinformatics analysis, ceRNA regulatory network