揭示CTGF和APOA1:扩张型心肌病的关键中枢基因和治疗靶点
Unveiling CTGF and APOA1: key hub genes and therapeutic targets in dilated cardiomyopathy.
Unveiling CTGF and APOA1: key hub genes and therapeutic targets in dilated cardiomyopathy.
扩张型心肌病(DCM)是一种危及生命的心血管疾病,影响超过0.04%的普通人群。然而,与DCM相关的关键基因仍不清楚。从基因表达综合数据库(GEO)获取了三个公开数据集(GSE120895、GSE53081和GSE42955)。对这些差异表达基因(DEGs)进行了加权基因共表达网络分析(WGCNA)、基因本体论(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。随后构建了蛋白质-蛋白质相互作用(PPI)网络以筛选核心基因。通过整合生物信息学方法鉴定出862个差异表达基因(DEGs)。WGCNA表明,蓝色和蓝绿色模块中的DEGs与DCM风险的关联最强(蓝色模块:r = 0.29,P = 2.5e-4;蓝绿色模块:r = 0.25,P = 1.6e-3)。对核心基因的KEGG通路富集分析显示,RTK-RAS通路评分与DCM风险相关。受试者工作特征(ROC)分析显示,CTGF和APOA1的表达水平可作为DCM风险的敏感且特异的预测指标(CTGF的AUC = 0.83,P = 0.002;APOA1的AUC = 0.867,P = 0.001)。此外,通过Western blot证实了CTGF和APOA1的表达。我们的结果表明,CTGF和APOA1与DCM风险相关,是值得进一步研究的潜在生物标志物。这些核心基因的鉴定及所涉及的RTK-RAS通路为未来DCM的功能研究提供了假设和方向。
Dilated cardiomyopathy (DCM), a life-threatening cardiovascular disease, affects more than 0.04% of the general population. However, the key genes associated with DCM are still unknown. Three publicly available datasets (GSE120895, GSE53081, and GSE42955) were obtained from the Gene Expression Omnibus (GEO) database. Weighted correlation network analysis (WGCNA), gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on these DEGs. A protein‒protein interaction (PPI) network was then constructed to select the hub genes. 862 differentially expressed genes (DEGs) were identified using an integrated bioinformatics approach. WGCNA indicated that DEGs in the blue and turquoise modules exhibited the strongest associations with DCM risk (blue module: r = 0.29, P = 2.5e-4; turquoise module: r = 0.25, P = 1.6e-3). KEGG pathway enrichment analysis of the hub genes revealed that the RTK-RAS pathway score was associated with DCM risk. Receiver operating characteristic (ROC) analysis revealed that the expression levels of CTGF and APOA1 may serve as sensitive and specific predictors of DCM risk (AUC of CTGF = 0.83, P = 0.002; AUC of APOA1 = 0.867, P = 0.001). Furthermore, the expression of CTGF and APOA1 was confirmed by Western blot. Our results revealed that CTGF and APOA1 are correlated with DCM risk and represent potential biomarkers worthy of further investigation. The identification of these hub genes and the implicated RTK-RAS pathway provides a hypothesis and a direction for future functional research on DCM.
Ran Wang, Jinmeng Chen, Jian Zhu, Xianlin Zhang, Xiaomei Li, Yiyao Jiang, et al. Unveiling CTGF and APOA1: key hub genes and therapeutic targets in dilated cardiomyopathy.. Journal of cardiothoracic surgery. 2026; doi:10.1186/s13019-026-04260-0.
Ran Wang, Jinmeng Chen, Jian Zhu, Xianlin Zhang, Xiaomei Li, Yiyao Jiang, et al (2026). Unveiling CTGF and APOA1: key hub genes and therapeutic targets in dilated cardiomyopathy.. Journal of cardiothoracic surgery. https://doi.org/10.1186/s13019-026-04260-0
Ran Wang, Jinmeng Chen, Jian Zhu, Xianlin Zhang, Xiaomei Li, Yiyao Jiang, et al. Unveiling CTGF and APOA1: key hub genes and therapeutic targets in dilated cardiomyopathy.[J]. Journal of cardiothoracic surgery, 2026 doi:10.1186/s13019-026-04260-0.
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