Bioinformatics Screening Of Hypertrophic Cardiomyopathy-Related Genes And Verification In Clinical Specimen

Objective:The objective of this study was to screen out the hub genes of hypertrophic cardiomyopathy and verify these genes in clinical specimen,in order to provide a theoretical basis for the study of the pathogenesis of hypertrophic cardiomyopathy.Methods:The high-throughput sequencing dataset GSE36961,which includes 106 cases of hypertrophic cardiomyopathy and 39 cases of control group,was searched in GEO database.The differentially-expressed genes(DEGs)between hypertrophic cardiomyopathy and normal tissues were analyzed by R software,and the weighted co-expression network of DEGs was constructed by "WGCNA package" to identify the modules related to hypertrophic cardiomyopathy.Functional enrichment analysis including GO analysis and KEGG analysis were used in the genes of the module,and the STRING database was used to construct the protein-protein interaction network,so as to screen out the hub genes.The 10 hub genes were then verified in the myocardial tissues of patients with hypertrophic cardiomyopathy and normal people.And finally,the target genes were screened out.Results:A total of 8002 DEGs were screened from the high-throughput sequencing data(P<0.05).The weighted co-expression network of DEGs was constructed by WGCNA,and two modules related to hypertrophic cardiomyopathy were screned,which were cyan module(Pearson cor=0.77,P=4e-29)and the magenta module(Pearson cor=0.76,p=2e-28).The gene function in the cyan module is mainly enriched in energy metabolism,and the gene function in the magenta module is mainly enriched in angiogenesis.32 genes and 157 protein-protein interactions were obtained by protein-protein interaction network analysis,and then we screened out the hub genes which were APP、DYNC1H1、FPR2、GNB1、CHRM2、CD59、ARPC2、GNG7、AP2M1、HSP90B1.The 10 hub genes were then verified in the myocardial tissues of patients with hypertrophic cardiomyopathy and normal people.Through the experiment of quantitative PCR detection,Western blotting detection and immunohistochemical detection,FPR2,CD59,ARPC2 and AP2M1 were screened out as target genes.It was found out that there was statistically-significant difference in the expression of FPR2,CD59,ARPC2 and AP2M1 between the two groups.Between these two groups,the expression of FPR2,CD59 and ARPC2 were decreased in the myocardial tissue of patients with HCM,while the expression of AP2M1 was increased in the myocardial tissue of patients with HCM.Conclusions:In this study,we obtained the differentially-expressed genes of hypertrophic cardiomyopathy by bioinformatics-analyzing the high-throughput sequencing dataset GSE36961 from GEO database.It was found out that 10 hub genes,which were APP,DYNC1H1,FPR2,GNB1,CHRM2,CD59,ARPC2,GNG7,AP2M1 and HSP90B1,were associated with hypertrophic cardiomyopathy.Through clinical specimen verification,it was found out that the expression of FPR2,CD59 and ARPC2 were decreased while the expression of AP2M1 was increased in the myocardium of patients with HCM.The results of this study will be helpful to clarify the pathogenesis of hypertrophic cardiomyopathy.