Identification of novel key genes and signaling pathways in hypertrophic cardiomyopathy: evidence from bioinformatics and next generation sequencing data analysis

Abstract

Hypertrophic cardiomyopathy (HCM) is a global health problem characterized by left ventricle become thick and stiff with effect of indication including chest pain, fluttering, fainting and shortness of breath. In this investigation, we aimed to identify diagnostic markers and analyzed the therapeutic potential of essential genes. Next generation sequencing (NGS) dataset GSE180313 was obtained from the Gene Expression Omnibus (GEO) database and used to identify differentially expressed genes (DEGs) in HCM. DEGs were screened using the DESeq2 Rbioconductor tool. Then, Gene Ontology (GO) and REACTOME pathway enrichment analyses were performed. Moreover, a protein-protein interaction (PPI) network of the DEGs was constructed, and module analysis was performed. Next, miRNA-hub gene regulatory network and TF-hub gene regulatory network were constructed and analyzed. Finally, diagnostic values of hub genes were assessed by by receiver operating characteristic (ROC) curve analysis. By performing DEGs analysis, total 958 DEGs ( 479 up regulated genes and 479 down regulated genes) were successfully identified from GSE180313, respectively. GO and REACTOME pathway enrichment analyses revealed that GO functions and signaling pathways were significantly enriched including response to stimulus, multicellular organismal process, metabolism and extracellular matrix organization. The hub genes of FN1, SOX2, TUBA4A, RPS2, TUBA1C, ESR1, SNCA, LCK, PAK1 and APLNR might be associated with HCM. The hub gens of FN1 and TPM3, together with corresponding predicted miRNAs (e.g., hsa-mir-374a-5p and hsa-miR-8052), and SH3KBP1 and ESR1 together with corresponding predicted TFs (e.g PRRX2 and STAT3) were found to be significantly correlated with HCM. This investigation could serve as a basis for further understanding the molecular pathogenesis and potential therapeutic targets of HCM.