School of Basic Medical Sciences, Shaanxi University of Chinese Medicine, Xianyang, 712046, China.
University of Southern California, Los Angeles, CA, 90089, USA.
Biol Res. 2023 Aug 9;56(1):45. doi: 10.1186/s40659-023-00451-4.
Hypertrophic 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.
Firstly, 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.
In 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.
Based 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.
肥厚型心肌病（HCM）是一种常染色体显性遗传病，是全球青少年和运动员猝死的主要原因。缺氧和免疫因素已被揭示与 HCM 的病理学有关。越来越多的证据表明，缺氧和炎症在 HCM 的病理学中作为触发因素和增强因素起作用。然而，缺氧和免疫相关基因在 HCM 中的作用尚未报道。
首先，我们从基因表达综合数据库（GEO）中获得了四个与 HCM 相关的数据集，用于差异表达分析。然后，通过微环境细胞群体计数器（MCP-counter）算法筛选在正常样本和 HCM 中显著表达的免疫细胞。接下来，通过 LASSO+支持向量机递归特征消除（SVM-RFE）和加权基因共表达网络分析（WGCNA）筛选缺氧和免疫相关基因。然后进行单基因富集分析和关键基因的表达验证。最后，构建关键基因的竞争性内源性 RNA（ceRNA）网络。
本研究发现了 35 个差异表达的缺氧基因。通过 LASSO+SVM-RFE 分析，进一步确定了 10 个具有差异表达缺氧基因的靶点。MCP-count 算法得到了 5 种差异表达的免疫细胞，经过 WGCNA 特征评估，发现了 612 个免疫基因。当将缺氧和免疫基因进行交叉制表分析时，鉴定出了三个与缺氧和免疫相关的基因（ATP2A2、DDAH1 和 OMA1）。
基于缺氧特征基因，鉴定出了三个关键基因。这些基因也与免疫激活显著相关，为研究 HCM 与缺氧和免疫之间的关系提供了理论依据和参考价值。
