Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People's Republic of China.
Medicine (Baltimore). 2023 Mar 3;102(9):e32627. doi: 10.1097/MD.0000000000032627.
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.
高血压（HT）是世界上最常见的心血管疾病之一，也是中风、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 相关的免疫生物标志物。在这项研究中，从基因表达谱数据集（GSE74144）下载了来自基因表达综合数据库（Gene Expression Omnibus database）的 RNA 测序数据。使用软件 limma 确定 HT 与正常样本之间的差异表达基因。筛选与 HT 相关的免疫相关基因。使用 R 包中的程序“clusterProfiler”进行基因本体论和京都基因与基因组百科全书通路富集分析。根据 STRING 数据库中的信息构建这些差异表达免疫相关基因（DEIRGs）的蛋白质-蛋白质相互作用网络。最后，使用 miRNet 软件预测和构建 TF-hub 和 miRNA-hub 基因调控网络。在 HT 中观察到 59 个 DEIRGs。基因本体论分析表明，DEIRGs 主要富集于胞质钙离子的正调控、肽激素、蛋白激酶 B 信号转导和淋巴细胞分化。京都基因与基因组百科全书富集分析表明，这些 DEIRGs 显著参与了 IgA 产生的肠道免疫网络、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疱疹病毒感染等。从蛋白质-蛋白质相互作用网络中，鉴定出 5 个枢纽基因（胰岛素样生长因子 2、细胞因子诱导的Src 同源 2 包含蛋白、细胞因子信号转导抑制因子 1、周期蛋白依赖性激酶抑制剂 2A 和表皮生长因子受体）。在 GSE74144 中进行了受试者工作特征曲线分析，所有曲线下面积大于 0.7 的基因均被鉴定为诊断基因。此外，构建了 miRNA-mRNA 和 TF-mRNA 调控网络。我们的研究在 HT 患者中确定了 5 个免疫相关的枢纽基因，并表明它们可能是 HT 的诊断生物标志物。
