Based On Differential Gene Analysis Combined With Weighted Gene Co-expression Network Analysis To Explore The Pathogenesis Of Obesity-related Diabetes

Objective:Exploring the mechanism of the occurrence and development of obesity-related diabetes by bioinformatics methods and searching for its potential biomarkers and therapeutic targets.Method:1.Retrieve the gene expression profile data(GSE71416)related to "Type 2diabetes AND Adipose tissue AND Homo sapiens" from GEO database.Screening of differentially expressed genes in obesity-related diabetes through R’s limma package(pacage).Use R’s WGCNA package to construct modules,and perform correlation analysis between modules and clinical traits,and find the module with the greatest correlation with clinical traits as the target for subsequent analysis.2.Use the DAVID online analysis tool to perform GO function enrichment and KEGG pathway enrichment for obesity-related diabetes differentially expressed genes and genes in target modules.3.Use the STRING online analysis tool to analyze the protein interaction of obesity-related diabetes differentially expressed genes.At the same time,export the edge file analyzed by WGCNA,use Cytoscape to draw the protein interaction network diagram,and identify the key genes of obesity-related diabetes through the Cyto Hubba plug-in.4.The two key gene sets obtained through the differentially expressed genes analysis approach and the WGCNA analysis approach were selected to intersect,and the key genes shared by the two were used for subsequent analysis.Results:1.1 GO enrichment analysis of differentially expressed genes:(1)The GO analysis of molecular functions shows that these differentially expressed genes have cell adhesion molecule binding activity,CXCR chemokine receptor binding,chemokine activity,fibroblast growth factor receptor binding,molecular functions such as activity,protein binding activity,Toll-like receptor 4 binding activity,and arachidonic acid binding activity.(2)GO analysis of cell components found that these genes are mainly located in the exosomes,extracellular regions,endoplasmic reticulum cavity,extracellular matrix,outer cell membrane surface,intercellular junctions and other parts of the cell.(3)In the GO analysis of the biological process,it was found that the differentially expressed genes are mainly involved in angiogenesis,immune response,cell chemotaxis,neutrophil chemotaxis,leukocyte migration,inflammatory response,external apoptosis signal pathway,and determination of protein in positioning on the plasma membrane,positive regulation of cell growth,inflammation,microvilli assembly,interleukin-2 biosynthesis,tumor necrosis factor-mediated signaling pathway,neutrophil aggregation,positive regulation of epithelial cell proliferation,reaction to lipopolysaccharide and other functions,fibroblast growth factor receptor signaling pathway and other processes.1.2 Analysis of KEGG enrichment of differentially expressed genes: There are a total of 10 pathways enriched by KEGG,including the Hippo signaling pathway,the interaction of viral proteins with cytokines and cytokine receptors,TNF signaling pathways,malaria,rheumatoid arthritis,IL-17 signaling pathway,cytokine and cytokine receptor interaction,gastric cancer,tight junctions,legionnaires disease,NF-κB signaling pathway.2.1 GO enrichment analysis of modular genes: GO analysis of the molecular functions of the genes in the module green shows that these genes have poly(A)RNA binding activity and cadherin binding participates in the intercellular adhesion function.For GO analysis of cellular components,these genes are located in nucleoli,mitochondrial nucleotides,cell-cell adhesion junctions and other locations.In GO analysis of biological processes,these genes are mainly involved in protein stabilization,active regulation of the mitotic cell cycle,intercellular adhesion,and regulation of translation.2.2 Analysis of KEGG enrichment of modular genes: There are a total of 10 pathways enriched by KEGG,including the longevity regulatory pathway,insulin signaling pathway,mTOR signaling pathway,tuberculosis,homologous recombina-tion,basic transcription factors,and PI3K-Akt signaling pathway.3.1 Hub genes of differentially expressed genes: A total of 10 genes,namely:CCL2,VCAM1,CXCL1,IL18,CDH1,CXCL6,CXCL3,KRT18,KRT8,TIMP1,are all down-regulated genes.3.2 Hub genes of WGCNA: A total of 20 genes,namely: PRPF19,SNRPD1,SRSF5,SRSF7,SF3B6,NCBP2,POLR2 K,HNRNPF(downregulation),NUDT21,FUS(downregulation),PPIL4,PQBP1,MMP2,IGF1,CDH1,MAPK8,CCL2,VCAM1,CXCL1,CTGF.4.Screened target genes: CXCL1,CCL2,VCAM1,CDH1,all of which are down-regulated genes.5.(1)There is no intersection between the gene set of the module green and the hub gene set of the WGCNA group and the WGCNA group.(2)There is no difference gene among the genes of module green.(3)Module green is negatively correlated with obese people suffering from diabetes,with a correlation coefficient of 0.6.When the function of module green decreases,the more likely it is to develop diabetes.Conclusions:1.196 differentially expressed genes were identified,among which the expression changes of CXCL1,CCL2,VCAM1,and CDH1 may be biomarkers for the development of obesity to diabetes.2.The PI3K-Akt-mTOR signaling pathway may be the key pathway for the development of morbid obesity to diabetes.3.The two genes TSC1 and EIF4 F can be used as key targets to regulate the PI3K-Akt-mTOR signaling pathway.