Identification of biomarkers correlated with hypertrophic cardiomyopathy with co-expression analysis
Identification of biomarkers correlated with hypertrophic cardiomyopathy with co-expression analysis
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通过共表达分析鉴定与肥厚型心肌病相关的生物标志物
DOI：
10.1002/jcp.28762
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发表时间：
2019-12-01
影响因子：
5.6
通讯作者：
Shan, Qijun
中科院分区：
文献类型：
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作者：
Chen, Ran;Ge, Tiantian;Shan, Qijun
肥厚型心肌病（HCM）是最常见的遗传性心脏病。为了确定与HCM患者临床预后相关的关键模块和候选生物标志物，我们进行了这项研究与共表达分析。为了构建与HCM相关的hub基因共表达网络，进行了加权基因共表达网络分析（WGCNA）。基因本体（GO）和京都基因和基因组百科全书（KEGG）富集分析通过注释、可视化和集成发现数据库（大卫）进行。通过对中心基因蛋白质相互作用网络的分析，识别了中心基因之间的相互作用。进行基因集富集分析以发现枢纽基因促进的途径所涉及的可能机制。为了验证枢纽基因，进行定量实时聚合酶链反应（RT-PCR）。基于拓扑重叠度量的聚类结果，鉴定了2，351个差异表达基因（DEG）。这些基因包含在六个不同的模块中。在这些模块中，黄色和蓝色模块显示出与HCM的关键相关性。DEG富含免疫系统程序相关的GO术语和KEGG途径。我们鉴定了9个中枢基因（TYROBP、STAT 3、CSF 1 R、ITGAM、SYK、ITGB 2、LILRB 2、林恩和HCK）显著影响免疫系统。在我们用RT-PCR验证的基因中，TYROBP、CSF 1 R和SYK在模型HCM大鼠中的表达水平显著增加。总之，我们确定了两个模块和9个枢纽基因，这是显着相关的HCM。我们发现免疫系统在HCM中可能起着至关重要的作用。因此，这些基因和通路可能成为未来具有临床实用性的治疗靶点。
Hypertrophic cardiomyopathy (HCM) is reported to be the most common genetic heart disease. To identify key module and candidate biomarkers correlated with clinical prognosis of patients with HCM, we carried out this study with co-expression analysis. To construct a co-expression network of hub genes correlated with HCM, the Weighted Gene Co-expression Network Analysis (WGCNA) was performed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed by Database for Annotation, Visualization and Integrated Discovery (DAVID). The protein-protein interaction network analysis of central genes was performed to recognize the interactions of central genes. Gene set enrichment analyses were carried out to discover the possible mechanisms involved in the pathways promoted by hub genes. To validate the hub genes, quantitative real-time polymerase chain reaction (RT-PCR) was performed. Based on the results of topological overlap measure based clustering, 2,351 differentially expressed genes (DEGs) were identified. Those genes were included in six different modules. Of these modules, the yellow and the blue modules showed a pivotal correlation with HCM. DEGs were enriched in immune system procedure associated GO terms and KEGG pathways. We identified nine hub genes (TYROBP, STAT3, CSF1R, ITGAM, SYK, ITGB2, LILRB2, LYN, and HCK) affected the immune system significantly. Among the genes we validated with RT-PCR, TYROBP, CSF1R, and SYK showed significant increasing expression levels in model HCM rats. In conclusion, we identified two modules and nine hub genes, which were prominently associated with HCM. We found that immune system may play a crucial role in the HCM. Accordingly, those genes and pathways might become therapeutic targets with clinical usefulness in the future.