Research Center for High Altitude Medicine, Key Laboratory of High Altitude Medicine (Ministry of Education), Key Laboratory of Application and Foundation for High Altitude Medicine Research in Qinghai Province (Qinghai-Utah Joint Research Key Lab for High Altitude Medicine), Qinghai University, Xining 810000, China.
Department of Clinical Medicine, Qinghai Institute of Health Sciences, Xining 810000, China.
Exp Biol Med (Maywood). 2023 Feb;248(3):217-231. doi: 10.1177/15353702221147557. Epub 2023 Feb 5.
Pulmonary hypertension (PH) is a cardiopulmonary vascular disease that acutely endangers human health and can be fatal. It progresses rapidly and has a high mortality rate. Its pathophysiology is complicated and still not completely elucidated; therefore, achieving treatment breakthroughs are difficult. In this study, data from 58 normal controls and 135 patients with PH were extracted from the GSE24988, GSE113439, and GSE117261 datasets in the Gene Expression Omnibus (GEO) database and screened for differentially expressed genes (DEGs). In addition, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Weighted gene co-expression network analysis (WGCNA) was used to identify the key modules and hub genes associated with PH. Eight PH-associated hub genes were identified. Furthermore, correlation analysis between immune cell infiltration and hub genes was performed, and the receiver operating characteristic (ROC) curves showed that had the best diagnostic efficacy. Moreover, a rat hypoxic pulmonary hypertension (HPH) model was generated, and the expression of hub genes in the lungs and pulmonary arteries of HPH rats was verified using western blotting assays. Our results showed that , , , , , and were highly expressed in the lungs. In addition, , , , , , and were significantly upregulated, whereas was significantly downregulated in the pulmonary arteries of HPH rats compared with those of controls. In conclusion, we identified PH hub genes with diagnostic and predictive value by performing WGCNA on data from the GEO database. Furthermore, we provided novel insights of PH that might be utilized to evaluate potential biomarker genes and therapeutic targets.
肺动脉高压(PH)是一种危害人类健康的心肺血管疾病,可导致急性发病,甚至危及生命。其病情进展迅速,死亡率高,发病机制复杂,尚未完全阐明,因此难以取得治疗突破。本研究从基因表达综合数据库(GEO)的 GSE24988、GSE113439 和 GSE117261 数据集提取 58 例正常对照和 135 例 PH 患者的数据,筛选差异表达基因(DEGs),并进行基因本体(GO)和京都基因与基因组百科全书(KEGG)通路富集分析。采用加权基因共表达网络分析(WGCNA)识别与 PH 相关的关键模块和枢纽基因。鉴定出 8 个与 PH 相关的枢纽基因。进一步对枢纽基因与免疫细胞浸润的相关性进行分析,ROC 曲线显示在诊断 PH 中具有最佳效果。此外,构建大鼠低氧性肺动脉高压(HPH)模型,通过 Western blot 检测 HPH 大鼠肺部和肺动脉中枢纽基因的表达。结果表明,在肺部, 、 、 、 、 和 表达上调;在肺动脉中, 、 、 、 、 、 和 表达上调, 表达下调。综上,本研究通过对 GEO 数据库数据进行 WGCNA,鉴定出具有诊断和预测价值的 PH 枢纽基因,并为评估潜在的生物标志物基因和治疗靶点提供了新的思路。