Functional Gene Module Study Of Ulcerative Colitis And Its Complications Based On WGCNA Analysis

Ulcerative colitis(UC)is a chronic inflammatory disease of intestinal tract caused by genetic susceptibility and abnormalities of the immune system.It is mainly characterized by long-term chronic recurrence of mucosal ulcerative lesions in the colon,and is collectively referred to as Inflammatory Bowel Disease(IBD)together with Crohn’s disease.The first effective drug for the treatment of ulcerative colitis is only glucocorticoids,especially for the acute exacerbation of the course of ulcerative colitis.However,some patients have resistance to hormonal therapy leading to ineffectiveness of glucocorticoid therapy.Prolonged ulcerative colitis can lead to a variety of complications,with the most serious consequences of colorectal epithelial carcinogenesis.The process of ulcerative colitis leading to colorectal epithelial carcinogenesis often takes more than a decade,and the pathological mechanism is very complicated,a series of changes,from various epigenetic modifications produced by genetic material to transduction disorders of signaling pathways,may have important implications in the progression of ulcerative colitis related colorectal cancer(UCRCC).Epidemiological studies have found that ulcerative colitis-related colorectal cancer still has a certain degree of difference in the pathogenesis and incidence of sporadic colorectal cancer.Colonization of colorectal cancer caused by prolonged ulcerative colitis may be associated with long-term effects of the chronic inflammatory immune microenvironment of the intestine,which has developed from normal epithelial tissue,low dysplasia,high dysplasia to cancer A process,but the current research on its specific molecular mechanism remains to be explored.The original intention of this study is based on an epidemiological investigation that the incidence of ulcerative colitis is increasing year by year and its canceration trend is increasing year by year.It can be concluded that ulcerative colitis-related colorectal cancer is the primary cancer of colorectal cancer in the future.The factor map may have a large proportion.In the research process of chronic intestinal inflammation and its complication mechanism,the dynamic continuity of research content has been an important factor restricting the mechanism of malignant transformation of chronic intestinal inflammation.In response to this goal,this study used the weighted gene co-expression network analysis(WGCNA)as the main way to break through this constraint.Traditional differential genetic analysis studies have different levels of batch differences and sensitivity of statistical analysis methods,resulting in different intestinal gene markers in different studies,which can not meet the needs of basic medical research and clinical transformation.The analysis of WGCNA algorithm based on bioinformatics effectively overcomes these shortcomings.As a system biology tool for studying gene expression-traits of sample,WGCNA algorithm has been widely used in disease disease typing and specific molecular mechanisms.A number of studies have used WGCNA analysis to find the node molecules in the gene co-expression network module,and these node molecules have proved to be key molecules in the gene network module in subsequent experimental verification.Due to the heterogeneity of the gut genome in the different stages of chronic intestinal inflammation,the use of WGCNA analysis can effectively remove the heterogeneous genome and systematically describe the relationship between disease phenotype and gene network cluster.Indicate the direction for subsequent experimental analysis verification.In the previous study,we used the WGCNA analysis method to study the expression profile chip and the normal tissue expression profile of the three groups of ulcerative colitis patients in different stages of the GEO database,the endogenous molecular regulatory network model of intestinal chronic inflammation was constructed by analyzing the expression profile chip data.At the genetic level,follistatin-like protein 1(FSTL1)was significantly up-regulated in the intestinal mucosa of patients with ulcerative colitis,and was significantly positively correlated with the degree of inflammation in patients with ulcerative colitis.Therefore,we conclude that FSTL1 may be involved in the activation of the inflammatory pathway during the active phase of ulcerative colitis.To test our hypothesis that FSTL1 may play an important role in the development and progression of patients with ulcerative colitis,we used DSS-induced mouse colitis model to study the relationship between the expression of FSTL1 and the active period of ulcerative colitis.First,we successfully constructed a mouse colitis model,and further used the mouse DSS colitis model and the inflammatory active mouse model to study the role of FSTL1 in the intestine.Through in vivo experiments,we found that FSTL1 is highly expressed in chronic intestinal inflammation,which may promote the progression of inflammation and inflammation-related carcinogenesis to some extent.The results of this study will provide additional clues for subsequent investigations into the pathogenesis of inflammatory activation and malignant complications of ulcerative colitis.