Zheng Xifeng, Liu Guangyan, Huang Ruina
Department of Geriatrics, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Department of Cardiology, Affiliated Hospital of Guangdong Medical University, Zhanjiang, China.
Front Cardiovasc Med. 2021 Oct 26;8:752559. doi: 10.3389/fcvm.2021.752559. eCollection 2021.
To identify feature immune-related genes (IRGs) in patients with hypertrophic cardiomyopathy (HCM) and verify their ability to diagnose HCM. The GSE160997 dataset on cardiac tissue from 18 HCM patients and 5 controls was downloaded from the Gene Expression Omnibus database. A false discovery rate <0.05 and |log2 fold change| >1 were the filters applied to identify the differentially expressed genes (DEGs). The differentially expressed IRGs were the intersection results between the DEGs and an IRG dataset from the IMMPORT database. The protein-protein interaction network of differentially expressed IRGs was constructed, and the top 20 hub genes with the most adjacent nodes in the network were selected. The least absolute shrinkage and selection operator regression algorithm and a random forest algorithm were used to identify the feature IRGs as biomarkers that were then verified against GSE36961. A total of 1079 DEGs were identified in GSE160997. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses indicated that immune-related mechanisms play an important role in the pathogenesis of HCM. A total of 121 differentially expressed IRGs were identified, and 5 feature IRGs were selected, 4 of which were confirmed as potential biomarkers of HCM by external verification with excellent discrimination ability. A diagnosis model of HCM based on the four feature IRGs was developed and visualized as a nomogram with a C-index of 0.925 (95% confidence interval 0.869-0.981). Our study identified four feature IRGs as biomarkers for the diagnosis of HCM, offering an innovative perspective of the underlying immune-related pathological molecular mechanisms.
识别肥厚型心肌病(HCM)患者中具有特征性的免疫相关基因(IRGs),并验证其诊断HCM的能力。从基因表达综合数据库下载了18例HCM患者和5例对照的心脏组织GSE160997数据集。应用错误发现率<0.05和|log2倍数变化|>1来筛选差异表达基因(DEGs)。差异表达的IRGs是DEGs与IMMPORT数据库中IRG数据集的交集结果。构建差异表达IRGs的蛋白质-蛋白质相互作用网络,并选择网络中相邻节点最多的前20个枢纽基因。使用最小绝对收缩和选择算子回归算法以及随机森林算法来识别作为生物标志物的特征IRGs,然后针对GSE36961进行验证。在GSE160997中总共鉴定出1079个DEGs。基因本体论和京都基因与基因组百科全书通路富集分析表明,免疫相关机制在HCM的发病机制中起重要作用。总共鉴定出121个差异表达的IRGs,并选择了5个特征IRGs,其中4个通过外部验证被确认为HCM的潜在生物标志物,具有出色的鉴别能力。基于这四个特征IRGs建立了HCM诊断模型,并将其可视化为列线图,C指数为0.925(95%置信区间0.869 - 0.981)。我们的研究确定了四个特征IRGs作为诊断HCM的生物标志物,为潜在的免疫相关病理分子机制提供了创新视角。