Abstract
Background. Accumulating evidence shows that the innate immune system is a key player in cardiovascular repair and regeneration, but little is known about the role of immune-related genes (IRGs) in hypertrophic cardiomyopathy (HCM). Methods. The differential mRNA expression profiles of HCM samples were downloaded from the Gene Expression Omnibus (GEO) dataset (GSE89714), and the IRG expression profile was obtained from the ImmPort database. The regulatory pathways of IRGs in HCM were screened out through discrepantly expressive genes (DEGs) analysis, enrichment of gene function/pathway analysis, and protein-protein interaction (PPI) network. Besides, hub IRGs in the PPI network were selected for drug prediction. Results. A total of 854 genes were differentially expressed in HCM, of which 88 were IRGs. Functional enrichment analysis revealed that 88 IRGs were mainly involved in the biological processes (BP) of SMAD protein pathway, smooth muscle cell proliferation, protein serine/threonine kinase, and mitogen-activated protein kinase (MAPK) cascade. Cytokine-cytokine receptor interaction, TGFβ signaling pathway, PI3K-Akt signaling pathway, and MAPK signaling pathway were enriched in the pathway enrichment analysis of these 88 IRGs. Furthermore, the PPI regulatory network of IRGs was constructed, and 10 hub IRGs were screened out to construct a regulatory network for HCM. 4 transcription factors (TFs) were the major regulator of 10 hub IRGs. Finally, these 10 hub IRGs were entered into the pharmacogenomics database for prediction, and the relevant drugs were obtained. Conclusions. In this study, 10 hub IRGs were coexpressed with 4 TFs to construct a regulatory network for HCM. Drug prediction of these 10 hub IRGs proposed potential therapeutic agents that could be used in HCM. These results indicate that IRGs are potential regulators and drug therapeutic targets in HCM.
Highlights
Cardiomyopathy refers to a myocardial disease with cardiac dysfunction, among which hypertrophic cardiomyopathy (HCM) is the most common
The abundance of 10 hub immune-related genes (IRGs) was screened, and these ten hub IRGs were used for drug prediction. These 10 hub IRGs were coexpressed with 4 transcription factors (TFs) to construct a regulatory network for HCM
After functional enrichment analysis of 854 discrepantly expressive genes (DEGs) in HCM, we found that these 854 DEGs mainly participated in 10 biological processes (BP), including extracellular matrix organization, extracellular structure organization, skeletal system development, ossification, collagen fibril organization, urogenital system development, axon development, bone development, connective tissue development, and renal system development (Figure 2(a))
Summary
Cardiomyopathy refers to a myocardial disease with cardiac dysfunction, among which hypertrophic cardiomyopathy (HCM) is the most common. Accumulating evidence shows that the innate immune system is a key player in cardiovascular repair and regeneration, but little is known about the role of immune-related genes (IRGs) in hypertrophic cardiomyopathy (HCM). 4 transcription factors (TFs) were the major regulator of 10 hub IRGs. the PPI regulatory network of IRGs was constructed, and 10 hub IRGs were screened out to construct a regulatory network for HCM. 10 hub IRGs were coexpressed with 4 TFs to construct a regulatory network for HCM. Drug prediction of these 10 hub IRGs proposed potential therapeutic agents that could be used in HCM. These results indicate that IRGs are potential regulators and drug therapeutic targets in HCM
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