Bioinformatics study of key genes and pathways in irritable bowel syn-drome with predominant diarrhea
Objective To explore key genes and pathways in irritable bowel syndrome with predominant diarrhea(IBS-D)based on bioinformatics analysis,and to provide potential molecular targets for its diagnosis and treatment.Methods The GSE212719 dataset in Gene Expression Omnibus was analyzed,GEO2R was used to identify differentially expressed genes(DEGs);Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analysis were performed through the DAVID database;proteinprotein interaction(PPI)network was constructed using STRING database,and Cytoscape 3.10.1 software screened the functional modules and key genes of IBS-D;bioinformatics platform of R language was used for gene set enrichment analysis(GSEA)and the top ten genes in the most significant gene set were analyzed,and finally the core pathway was established.Results A total of 182 DEGs were identified,including 94 up-regulated and 88 down-regulated genes;the top three sorted up-regulated genes were MT-ATP6,FSIP2,and FABP2,and the down-regulated genes were LOC112268284,COL13A1,and RNA5-8SN1.The results of GO enrichment analysis results showed that the mainly focused on the innate immune response in mucosa,nucleosome,and ribosome assembly.The results of KEGG pathway analysis showed that ribosomes,ribosome biogenesis in eukaryotes,and systemic lupus erythematosus were the major pathways.The PPI network map was jointly constructed by 44 nodes and 336 edges,and ten core Hub genes were found to be CDK1,TOP2A,CCNB1,KIF23,NDC80,CENPE,KNL1,ANLN,DEPDC1,and HMMR.GSEA found that the pathogenic pathway of IBS-D may be closely related to abnormal acid-base balance,increased serum lactate,lactic acidosis,mitochondrial abnormalities,and abnormal mitochondrial respiratory chain activity;the top ten genes in the most significant gene set were NDUFA12,SLC26A3,PIGA,UQCRB,NDUFAF4,TRMT10C,AC AT1,GFM2,PNPLA8,and NDUFA4.The key signal pathway centered on TOP2A and MT-ATP6.Conclusion The up-regulation of TOP2A and MT-ATP6 genes may be related to increase of serum lactic acid due to mitochondrial dysfunction,while the down-regulation of COL13A1 gene may cause structural damage and increased inflammation of intestinal muscle tissue,and these may be associated with the development of IBS-D.This comprehensive analysis provided key information on genes and pathways involved in IBS-D,providing new avenues for further research.
Irritable bowel syndrome with predominant diarrheaDifferentially expressed genesBioinformatics analysisGene Expression Omnibus
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