Screening Pathogenic Genes Of Right Heart Failure And Prediction Of Potential Therapeutic Drugs Based On Bioinformatics Analysis

Objective: To explore the key pathogenic genes of Right heart failure(RHF),and to predict the upstream transcription factors of the key pathogenic genes and the therapeutic drugs targeting the key pathogenic genes.Methods: GSE198618 data set was downloaded from Gene expression omnibus(GEO),which included 11 samples of compensated RHF,7 samples of decompensated RHF and 14 control samples.Differentially expressed genes(DEGs)were found by integrating the original data.Through Gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment,the biological function of the DEGs was analyzed.Protein-protein interaction(PPI)network was constructed by using STRING database,and key pathogenic genes were screened by using Cytoscape software Cyto Hubba plug-in.The diagnostic efficiency of key pathogenic genes was evaluated by receiver operating characteristic(ROC)curve,and the expression profile of key pathogenic genes was evaluated by t test.The upstream Transcription factor(TF)regulating key pathogenic genes was predicted by the plugin IRegulon of Cytoscape software,and the transcription factor-key pathogenic gene regulatory network was constructed.Using CMap database to predict potential therapeutic drugs targeting key pathogenic genes.Results: 115 DEGs were screened during the compensated RHF,including 25 up-regulated genes and 90 down-regulated genes.During the decompensated RHF,1311 DEGs were screened,including 861 up-regulated genes and 450 down-regulated genes.There are 81 DEGs shared in the compensated and decompensated RHF,and their biological functions mainly involve the response to external stimuli,cell chemotaxis,inflammatory response,IL-17 signaling pathway,TNF signaling pathway,ECM-receptor interaction,Cytokine-Cytokine receptor interaction pathway and so on.In the PPI network with DEGs,MMP9,POSTN,FOSL1,THBS1,NR4A1,SERPINE1,ATF3,CTGF,CXCL2 and IL6 have the highest connectivity,which are the core of the regulatory network and are the key pathogenic genes for the development of RHF.ROC curve analysis shows that these ten key pathogenic genes have high diagnostic value for RHF and can be used as therapeutic targets for RHF.t-test analysis showed that the expression profiles of these ten key pathogenic genes were significantly higher than those of the control group in the compensated and decompensated RHF,and the difference was statistically significant(P < 0.05).Transcription factor prediction showed that the expression of key pathogenic genes was regulated by upstream transcription factors MEF2 A and MEF2 C.The prediction results of CMap database show that Fostamatinib,Canertinib,AS-605240,TWS-119 and Atorvastatin are potential therapeutic drugs for the treatment of RHF.Conclusion:1.The abnormal expression and regulation of the key pathogenic genes MMP9,POSTN,FOSL1,THBS1,NR4A1,SERPINE1,ATF3,CTGF,CXCL2 and IL6 play an important role in the occurrence and development of RHF,and their regulation mainly involves signal receptor conduction and the regulation of structural components of extracellular matrix.2.Transcription factors MEF2 A and MEF2 C play a role in RHF by regulating the expression of key pathogenic genes NR4A1,SERPINE1,ATF3 and CTGF.3.Fostamatinib,Canertinib,AS-605240,TWS-119 and Atorvastatin are potential small molecule drugs for the treatment of RHF.