Transcriptomics data integration and analysis to uncover hallmark genes in hypertrophic cardiomyopathy

Introduction: Hypertrophic cardiomyopathy (HCM) is a heterogeneous disease that mainly affects the myocardium. In the current study, we aim to explore HCM-related hub genes through the analysis of differentially expressed genes (DEGs) between HCM and normal sample groups. Methods: The GSE68316 and GSE36961 expression profiles were obtained from the Gene Expression Omnibus (GEO) database for the identification of DEGs, to explore hub genes, and to perform their expression analysis. Clinical HCM and control tissue samples were taken for expression and promoter methylation validation analysis via RNA-sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) analyses. Then, other different bioinformatics tools were employed to perform STRING, lncRNA-miRNA-mRNA regulatory networks, gene enrichment, and drug prediction analyses. Results: In total, the top 20 DEGs, including 10 up-regulated and 10 down-regulated, were obtained from GSE68316. Out of the 20 DEGs, we subsequently identified the 8 most important hub genes including 5 up-regulated genes (EPB42, UQCRH, CA1, PFDN5, and LSM5) and 3 down-regulated genes (RPS24, TNS1, and RPL26). Expression and promoter methylation dysregulation of these genes were further validated on clinical HCM samples paired with controls. Next, we further investigated hub genes' regulatory 6 miRNAs (has-mir-1-3p, has-mir-129-5p, has-mir-16-5p, has-mir-23b-3p, hasmir-27-3p, and has-mir-182-5p) and miRNAs regulatory 4 lncRNAs (NUTMB2-AS1, NEAT1, XIST, and GABPB1-AS1) in this study via the lncRNA-cricRNA-miRNA-mRNA regulatory network. Later on, gene enrichment analysis revealed that hub genes were enriched in various important pathways including Nitrogen metabolism, Ribosome, RNA degradation, Cardiac muscle contraction, and Coronavirus disease, etc. Finally, the drug prediction analysis highlighted different potential candidate drugs for altering the expression of hub genes in the treatment of HCM. Conclusion: In summary, the identification of key hub genes and their enrichment analysis in the current study may shed light on the mechanisms behind the occurrence and development of HCM.