Identification of Pyroptosis-related Hub Genes and Potential Therapeutic Drugs in Cardiac Remodeling Based on GEO Database
Objective To explore the the pyroptosis-related hub genes in cardiac remodeling by bioinformatics methods from the perspective of pyroptosis,analyze their functions,predict possible therapeutic drugs,and provide theoretical basis for the diagnosis and treatment of cardiac remodeling.Methods The gene chip data set related to cardiac remodeling was downloaded from the Gene Expression Omnibus(GEO)database of the National Library of Medicine in the United States,and the differentially expressed genes(DEGs)related to cardiac remodeling were identified by GEO2R online analysis tool.The pyroptosis-related genes were collected in the GeneCards database,and the protein interaction network was constructed between the pyroptosis-related genes and the intersection genes of the above DEGs to identify the core genes.Metascape2.0 was used to perform GO and KEGG functional enrichment analysis on the intersection genes.Finally,the DGIdb database was used to predict the interaction between potential drugs and the above core genes.Results The dataset GSE24489 was screened out from the GEO database as a cardiac remodeling-related dataset,and 1767 cardiac remodeling-related DEGs were screened out from GSE24489 and intersected with the pyroptosis-related genes from the GeneCards database to obtain 45 pyroptosis-related DEGs in cardiac remodeling.GO analysis of these DEGs showed that biological processes were mainly enriched in the regulation of defense response,regulation of protein cleavage,inflammatory response,etc.KEGG pathway enrichment analysis showed that DEGs related to pyroptosis were mainly enriched in Alzheimer's disease,cancer pathway,hepatitis C,PI3K-Akt signaling pathway and so on.Nine cardiac remodeling-related hub DEGs(TLR3、PTGS2、CASP1、CASP8、GSK3β、VEGFA、MKI67)were identified from these pyroptosis-related DEGs.The results of the DGIdb database predicting the interaction between potential drugs and hub genes showed that drugs such as Nimesulide,Celecoxib,and GSK3β inhibitor Tideglusib might become key candidates for the treatment of cardiac remodeling.Conclusion These identified hub genes such as PTGS2 may play an important role in the occurrence and development of cardiac remodeling and represent new therapeutic targets for the treatment of heart remodeling.