Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing, 210006, China.
Department of Cardiology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
ESC Heart Fail. 2022 Apr;9(2):1370-1379. doi: 10.1002/ehf2.13827. Epub 2022 Feb 6.
AIMS: Heart failure (HF) is a chronic heart disease with a high incidence and mortality. Due to the regulatory complexity of gene coexpression networks, the underlying hub genes regulation in HF remain incompletely appreciated. We aimed to explore potential key modules and genes for HF using weighted gene coexpression network analysis (WGCNA). METHODS AND RESULTS: The expression profiles by high throughput sequencing of heart tissues samples from HF and non-HF samples were obtained from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between HF and non-HF samples were firstly identified. Then, a coexpression network was constructed to identify key modules and potential hub genes. The biological functions of potential hub genes were analysed by Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. Finally, a protein-protein interaction (PPI) network was constructed using the STRING online tool. A total of 135 DEGs (133 up-regulated and 2 down-regulated DEGs) between HF and non-HF samples were identified in the GSE135055 and GSE123976 datasets. Moreover, a total of 38 modules were screened based on WGCNA in the GSE135055 dataset, and six potential hub genes (UCK2, ASB1, CCNI, CUX1, IRX6, and STX16) were screened from the key module by setting the gene significance over 0.2 and the module membership over 0.8. Furthermore, 78 potential hub genes were obtained by taking the intersection of the 135 DEGs and all genes in the key module, and enrichment analysis revealed that they were mainly involved in the MAPK and PI3K-AKT signalling pathways. Finally, in a PPI network constructed with the 78 potential hub genes, CUX1 and ASB1 were identified as hub genes in HF because they were also identified as potential hub genes in the WGCNA. CONCLUSIONS: To the best of our knowledge, our study is the first to employ WGCNA to identify the key module and hub genes for HF. Our study identified a module and two genes that might play important roles in HF, which may provide potential biomarkers for the diagnosis of HF and improve our knowledge of the molecular mechanisms underlying HF.
目的：心力衰竭（HF）是一种发病率和死亡率均较高的慢性心脏病。由于基因共表达网络的调控复杂性，HF 中潜在的枢纽基因调控仍不完全清楚。我们旨在使用加权基因共表达网络分析（WGCNA）探索 HF 的潜在关键模块和基因。
方法和结果：从基因表达综合数据库中获取 HF 和非 HF 样本的心脏组织样本高通量测序的表达谱。首先鉴定 HF 和非 HF 样本之间的差异表达基因（DEG）。然后，构建共表达网络以识别关键模块和潜在的枢纽基因。通过基因本体论和京都基因与基因组百科全书途径富集分析分析潜在枢纽基因的生物学功能。最后，使用 STRING 在线工具构建蛋白质-蛋白质相互作用（PPI）网络。在 GSE135055 和 GSE123976 数据集中共鉴定出 135 个 DEG（133 个上调和 2 个下调的 DEG）。此外，基于 WGCNA 在 GSE135055 数据集中筛选出 38 个模块，并通过设置基因显著性>0.2 和模块成员>0.8，从关键模块中筛选出 6 个潜在的枢纽基因（UCK2、ASB1、CCNI、CUX1、IRX6 和 STX16）。此外，通过取 135 个 DEG 和关键模块中的所有基因的交集，获得了 78 个潜在的枢纽基因，富集分析表明它们主要参与 MAPK 和 PI3K-AKT 信号通路。最后，在使用 78 个潜在枢纽基因构建的 PPI 网络中，CUX1 和 ASB1 被鉴定为 HF 的枢纽基因，因为它们也被鉴定为 WGCNA 中的潜在枢纽基因。
结论：据我们所知，我们的研究首次使用 WGCNA 来识别 HF 的关键模块和枢纽基因。我们的研究鉴定出一个模块和两个可能在 HF 中发挥重要作用的基因，这可能为 HF 的诊断提供潜在的生物标志物，并提高我们对 HF 分子机制的认识。
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