Identification and analysis of key hypoxia- and immune-related genes in hypertrophic cardiomyopathy

Biological Research

Research Article

Zhao Dong¹  Lu Yu²  Heng Ma³  Yishi Wang³  Yue Yin³  Mujun Yu⁴  Linfang Du⁴  Zhuang Li⁵  Haozhen Yu⁵  Lanxin Gu⁶ 

[1] Department of General Practice, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an, China;Department of Pathology, Xijing Hospital, Fourth Military Medical University, 710032, Xi’an, China;Department of Physiology and Pathophysiology, School of Basic Medicine, Fourth Military Medical University, 710032, Xi’an, China;Medical School of Yan’an University, Yan’an University, 716000, Yan’an, China;School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, 712046, Xianyang, China;University of Southern California, 90089, Los Angeles, CA, USA;

关键词: Hypertrophic cardiomyopathy;    Hypoxia;    Immunity;    Hub gene;   

DOI  :  10.1186/s40659-023-00451-4

 received in 2023-03-20, accepted in 2023-06-29,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundHypertrophic cardiomyopathy (HCM), an autosomal dominant genetic disease, is the main cause of sudden death in adolescents and athletes globally. Hypoxia and immune factors have been revealed to be related to the pathology of HCM. There is growing evidence of a role for hypoxia and inflammation as triggers and enhancers in the pathology in HCM. However, the role of hypoxia- and immune-related genes in HCM have not been reported.MethodsFirstly, we obtained four HCM-related datasets from the Gene Expression Omnibus (GEO) database for differential expression analysis. Immune cells significantly expressed in normal samples and HCM were then screened by a microenvironmental cell population counter (MCP-counter) algorithm. Next, hypoxia- and immune-related genes were screened by the LASSO + support vector machine recursive feature elimination (SVM-RFE) and weighted gene co-expression network analysis (WGCNA). Single-gene enrichment analysis and expression validation of key genes were then performed. Finally, we constructed a competing endogenous RNA (ceRNA) network of key genes.ResultsIn this study, 35 differentially expressed hypoxia genes were found. By using LASSO + SVM-RFE analysis, 10 more targets with differentially expressed hypoxia genes were identified. The MCP-count algorithm yielded five differentially expressed immune cells, and after assessing them for WGCNA characteristics, 612 immune genes were discovered. When hypoxia and immune genes were combined for cross-tabulation analysis, three hypoxia- and immune-related genes (ATP2A2, DDAH1, and OMA1) were identified.ConclusionBased on hypoxia characteristic genes, three key genes were identified. These were also significantly related to immune activation, which proves a theoretical basis and reference value for studying the relationship between HCM and hypoxia and immunity.Graphical Abstract

【 授权许可】

CC BY   
© Sociedad de Biologia de Chile 2023

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