高血压患者免疫相关基因的调节机制。
Regulatory mechanism of immune-related genes in patients with hypertension.
发表日期:2023 Mar 03
作者:
Linhu Zhang, Wei Zhang, Jianling Chen
来源:
CYTOKINE & GROWTH FACTOR REVIEWS
摘要:
高血压(HT)是世界上最常见的心血管疾病之一,并且是中风、心肌梗死、心力衰竭和肾衰竭的重要危险因素。最近的研究表明,免疫系统的激活在HT的发生和维持中起着重要作用。因此,本研究旨在确定HT中的免疫相关生物标志物。在本研究中,从基因表达 Omnibus数据库下载了基因表达谱数据集(GSE74144)的RNA测序数据。使用limma软件识别HT和正常样本之间的差异表达基因。筛选与HT相关联的免疫相关基因。使用R包“clusterProfiler”进行基因本体论和Kyoto基因组学通道富集分析。根据STRING数据库中的信息构建这些差异表达的免疫相关基因(DEIRGs)的蛋白质互作网络。最后,使用miRNet软件预测和构建了TF-hub和miRNA-hub基因调控网络。观察到59个HT中的DEIRGs。基因本体论分析表明,DEIRGs主要富集在细胞质钙离子、肽类激素、蛋白激酶B信号和淋巴细胞分化的正调节上。Kyoto基因组学富集分析表明,这些DEIRGs显著参与肠道免疫网络IgA生产、自身免疫性甲状腺疾病、JAK-STAT信号通路、肝细胞癌和卡波西肉瘤相关的单纯疱疹病毒感染等。从蛋白质互作网络中确定了5个中枢基因(胰岛素样生长因子2、细胞因子诱导Src同源2含量蛋白、细胞因子抑制剂1、细胞周期依赖性激酶抑制剂2A和表皮生长因子受体)。在GSE74144中执行了ROC曲线分析,并将所有面积大于0.7的基因识别为诊断基因。此外,还构建了miRNA-mRNA和TF-mRNA调控网络。我们的研究确定了在HT患者中的5个免疫相关中枢基因,并证明它们可能是HT的潜在诊断生物标志物。版权所有©2023作者。由 Wolters Kluwer Health, Inc. 发布。
Hypertension (HT) is among the most common cardiovascular diseases in the world and is an important risk factor for stroke, myocardial infarction, heart failure, and kidney failure. Recent studies have demonstrated that activation of the immune system plays an important role in the occurrence and maintenance of HT. Thus, this research aimed to determine the immune-related biomarkers in HT. In this study, RNA sequencing data of the gene expression profiling datasets (GSE74144) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes between HT and normal samples were identified using the software limma. The immune-related genes associated with HT were screened. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were performed using the program "clusterProfiler" of the R package. The protein-protein interaction network of these differentially expressed immune-related genes (DEIRGs) was constructed based on the information from the STRING database. Finally, the TF-hub and miRNA-hub gene regulatory networks were predicted and constructed using the miRNet software. Fifty-nine DEIRGs were observed in HT. The Gene Ontology analysis indicated that DEIRGs were mainly enriched in the positive regulation of cytosolic calcium ions, peptide hormones, protein kinase B signaling, and lymphocyte differentiation. The Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that these DEIRGs were significantly involved in the intestinal immune network for IgA production, autoimmune thyroid disease, JAK-STAT signaling pathway, hepatocellular carcinoma, and Kaposi sarcoma-associated herpesvirus infection, among others. From the protein-protein interaction network, 5 hub genes (insulin-like growth factor 2, cytokine-inducible Src homology 2-containing protein, suppressor of cytokine signaling 1, cyclin-dependent kinase inhibitor 2A, and epidermal growth factor receptor) were identified. The receiver operating characteristic curve analysis was performed in GSE74144, and all genes with an area under the curve of > 0.7 were identified as the diagnostic genes. Moreover, miRNA-mRNA and TF-mRNA regulatory networks were constructed. Our study identified 5 immune-related hub genes in patients with HT and demonstrated that they were potential diagnostic biomarkers for HT.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.