Data Mining And Bioinformatics Analysis Of Gene Expression Profiles Of Hepatitis B-related Acute Liver Failure

Objective:To screen the hub genes that may be related to the occurrence and development of hepatitis B-associated acute liver failure?HBV-ALF?and analyze their potential biological function by using various bioinformatics analysis tools,so as to provide scientific basis for the diagnosis,treatment and prognosis of HBV-ALF.Methods:?1?Screening of differentially expressed genes?DEGs?:Gene expression profiling data GSE38941 was downloaded from NCBI's the Gene Expression Omnibus?GEO?database,and gene expression profile data were read,pre-processed and screened by using affy and limma of R.Differences in gene expression were expressed by fold change?FC?.The screening criteria were P<0.001,|log₂FC|?2.?2?Functional enrichment analysis of DEGs:DEGS were divided into up-regulated and down-regulated genes for statistical analysis.DAVID online analysis website was used for gene ontology?GO?enrichment analysis of the DEGs,KABOS online analysis website was used for KEGG biological pathway enrichment analysis of DEGs.?3?Interaction analysis of DEGs-encoded proteins:Protein-protein interaction?PPI?between DEGs-encoded proteins was analyzed by STRING online database,and visualized by CytoScape software.MCODE and BiNGO loaded in CytoScape software were used to construct and analyze functional modules.?4?Screening of hub genes:12 topological analysis methods in CytoHubba loaded in Cytoscape software were used to calculate the topological parameters of proteins in PPI network imported into CytoScape.Sort the parameters of the 12 algorithms from large to small and the top 50proteins expressed by DEGs were selected.Among the 12 algorithms,proteins ranked in the top 50 in 6 or more algorithms were considered as the hub genes.?5?Structural analysis of key hub genes and exploration of interaction relationship:The STRING database was used to construct the interaction relationship among the hub genes,and the NCBI,GenClip document mining database,neXtProt,EMBL-EBI,NetPhos3.1 and other databases were used to explore the function,the three-dimensional structures,the structure regions and the phosphorylation posion of the key hub genes.Results:?1?DEGs screening results:According to the screening criteria,a total of 828 DEGs were screened,compared with the control group,424 DEGs were down-regulated and 404 up-regulated.?2?Results of GO enrichment analysis:Cellular ComponentThe up-regulated genes in the cellular component were mainly enriched in the extracellular region,including extracellular exosome,membrane,extracellularspace,extracellularregion,etc.The down-regulated gene in the cellular component were mainly enriched in extracellular regions such as extracellular exosome,extracellular region,extracellular space,and also included in some components of the organelle such as endoplasmic reticulum membrane,intracellular membrane-bounded organelle,mitochondrial matrix,organelle membrane,etc.Biological ProcessThe up-regulated genes in the biological process were mainly enriched in inflammation and immune response,such as signal transduction,immune response,inflammatory response,innate immune response,cell adhesion,cell proliferation,etc.While the biological processes of down-regulated genes were mainly concentrated in metabolic redox and metabolic related processes,such as oxidation-reduction process,negative regulation of endopeptidase activity,xenobiotic metabolic process,lipid metabolic process,etc.Molecular FunctionThe up-regulated genes in the molecular function were enriched in three meaningful terms,including actin binding,extracellular matrix structural constituent and MHC class II receptor activity.The down-regulated genes in the molecular function were mainly enriched in some oxidatively related enzyme activities and binding reaction related items such as oxidoreductase activity,receptor binding,serine-type endopeptidase activity,heme binding,iron ion binding,monooxygenase activity,etc.?3?KEGG signal pathway enrichment analysis of DEGsUp-regulated DEGs were mainly enriched in signaling pathways related to inflammation and infection,such as cell adhesion molecules?CAMs?,HTLV-Iinfection,chemokinesignalingpathway,cytokine-cytokine receptor interaction,staphylococcus aureus infection,etc.The KEGG signaling pathway of down-regulated DEGs were mainly enriched in metabolism and P450 oxidation,such as metabolic pathways,complement and coagulation cascades,drug metabolism-cytochrome P450,metabolism of xenobiotics by cytochrome P450 and other terms.?4?A total of 17 hub genes that may be related to HBV-ALF,including 9 down-regulated DEGs,which are ALB,KNG1,VEGFA,C3,PLG,ACACB,IGF1,F2 and APOB,and 8 up-regulated DEGs,including CXCR4,CCR5,SYK,ITGB2,LCK,PIK3CG,ITGA2 and CSF1R.?5?The interaction of these 17 hub genes was constructed by STRING database.In the whole network,except for ACACB,the other 16genes constitute a complex interaction.CXCR4,VEGFA,ITGB2,PLG,F2,ALB and IGF1 were the most active genes.Conclusions:?1?A total of 828 DEGs were screened out,which indicated that the occurrence and development of HBV-ALF may be statistically associated with multiple genes.?2?The DEGs are mainly concentrated in extracellular regions and some components of organelles in cell components;in the biological processes,they are mainly enriched in inflammation,immune response,redox and metabolism-related processes;and in the molecular function,they are mainly enriched in actin binding,extracellular matrix structural components and MHC class receptor activity,as well as some oxidation related enzyme activities and binding reaction functions.?3?A total of 17 DEGs that may play an important role in the development of HBV-ALF.Among them,CXCR4,VEGFA,ITGB2,PLG,F2,ALB,and IGF1 have the most interactions which we called key hub genes.?4?CXCR4,VEGFA,ITGB2 and IGF1 are involved in the mechanism of disease development.They may be used as potential therapeutic targets for HBV-ALF if we carry out more in-depth research.PLG and ALB may be used as the disease progress judgment and prognosis index for HBV-ALF diseases,F2 gene is related to blood coagulation,and can be used as an indicator for judging the disease condition.