Idiopathic pulmonary arterial hypertension (IPAH) is a fatal cardiovascular disease event with significant morbidity and mortality. However, its potential molecular mechanisms and potential key genes have not been totally evaluated. The gene expression profile of GSE33463, including 30 individuals diagnosed with IPAH and 41 normal controls, was downloaded from Gene Expression Omnibus database. The differentially expressed genes (DEGs) were identified using limma package in R. Gene Ontology (GO) annotation, the Kyoto Encyclopedia of Genes and Genomes (KEGG) were carried out to get further insight into the possible functions of the identified DEGs. Then, the protein–protein interaction (PPI) network of all DEGs was constructed. Nodes with higher degree centrality (≥10) were considered as hub proteins in the PPI network. Area under the curve (AUC) values obtained from the receiver operating characteristic (ROC) curve analysis was utilized to assess the diagnostic effectiveness of hub genes in discriminating IPAH from normal individuals. Sixty-nine DEGs were identified, including 41 upregulated and 28 downregulated DEGs. The GO enrichment analysis indicated that genes were significantly enriched in oxygen carrier activity, oxygen binding, heme binding, molecular carrier activity, and antioxidant activity. KEGG pathway enrichment showed that genes were mainly involved in cytokine and cytokine receptor, Chemokine signaling pathway, interleukin-17 signaling pathway, and Toll-like receptor (TLR) signaling pathway. JUN, ALAS2, HBD, EPB42, TLR7, SLC4A1, and CXCR4 were identified as the hub genes nodes. The area under the ROC curve indicated that three hub genes have high diagnostic value in IPAH with AUC of 0.934 [95% confidence interval (CI): 0.849–0.979] in TLR7, 0.910 (95% CI: 0.818–0.965) in JUN, and 0.895 (95% CI: 0.800–0.955) in CXCR4. The identified candidate key genes and pathways help us understand the molecular mechanisms underlying the pathogenesis of IPAH. TLR7, JUN, and CXCR4 may be novel biomarkers in IPAH diagnosis.

中文翻译：

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通过综合生物信息学方法鉴定与特发性肺动脉高压相关的差异表达基因。

特发性肺动脉高压 (IPAH) 是一种致命的心血管疾病事件，具有显着的发病率和死亡率。然而，其潜在的分子机制和潜在的关键基因尚未完全评估。从基因表达综合数据库下载GSE33463基因表达谱，包括30例IPAH患者和41例正常对照。差异表达基因 (DEG) 使用 R. Gene Ontology (GO) 注释中的 limma 包进行鉴定，执行京都基因和基因组百科全书 (KEGG) 以进一步了解鉴定的 DEG 的可能功能。然后，构建了所有 DEG 的蛋白质 - 蛋白质相互作用（PPI）网络。具有较高度中心性（≥10）的节点被认为是 PPI 网络中的枢纽蛋白。从受试者工作特征 (ROC) 曲线分析获得的曲线下面积 (AUC) 值用于评估中枢基因在区分 IPAH 与正常个体方面的诊断有效性。鉴定出 69 个 DEG，包括 41 个上调和 28 个下调的 DEG。GO富集分析表明基因在氧载体活性、氧结合、血红素结合、分子载体活性和抗氧化活性方面显着富集。KEGG通路富集显示基因主要参与细胞因子和细胞因子受体、趋化因子信号通路、白细胞介素17信号通路和Toll样受体(TLR)信号通路。JUN、ALAS2、HBD、EPB42、TLR7、SLC4A1 和 CXCR4 被确定为枢纽基因节点。ROC 曲线下面积表明三个中枢基因在 IPAH 中具有很高的诊断价值，TLR7 中的 AUC 为 0.934 [95% 置信区间 (CI)：0.849-0.979]，6 月份为 0.910（95% CI：0.818-0.965），在 CXCR4 中为 0.895（95% CI：0.800–0.955）。确定的候选关键基因和通路有助于我们了解 IPAH 发病机制的分子机制。TLR7、JUN 和 CXCR4 可能是 IPAH 诊断中的新型生物标志物。