Department of cardiology, The second hospital of Jilin University, Changchun, China.
Department of cardiology, China-Japan Union Hospital of Jilin University, Changchun, China.
Respir Res. 2024 Aug 3;25(1):296. doi: 10.1186/s12931-024-02928-6.
Pulmonary arterial hypertension (PAH) is a life-threatening chronic cardiopulmonary disease. However, there is a paucity of studies that reflect the available biomarkers from separate gene expression profiles in PAH.
The GSE131793 and GSE113439 datasets were combined for subsequent analyses, and batch effects were removed. Bioinformatic analysis was then performed to identify differentially expressed genes (DEGs). Weighted gene co-expression network analysis (WGCNA) and a protein-protein interaction (PPI) network analysis were then used to further filter the hub genes. Functional enrichment analysis of the intersection genes was performed using Gene Ontology (GO), Disease Ontology (DO), Kyoto encyclopedia of genes and genomes (KEGG) and gene set enrichment analysis (GSEA). The expression level and diagnostic value of hub gene expression in pulmonary arterial hypertension (PAH) patients were also analyzed in the validation datasets GSE53408 and GSE22356. In addition, target gene expression was validated in the lungs of a monocrotaline (MCT)-induced pulmonary hypertension (PH) rat model and in the serum of PAH patients.
A total of 914 differentially expressed genes (DEGs) were identified, with 722 upregulated and 192 downregulated genes. The key module relevant to PAH was selected using WGCNA. By combining the DEGs and the key module of WGCNA, 807 genes were selected. Furthermore, protein-protein interaction (PPI) network analysis identified HSP90AA1, CD8A, HIF1A, CXCL8, EPRS1, POLR2B, TFRC, and PTGS2 as hub genes. The GSE53408 and GSE22356 datasets were used to evaluate the expression of TFRC, which also showed robust diagnostic value. According to GSEA enrichment analysis, PAH-relevant biological functions and pathways were enriched in patients with high TFRC levels. Furthermore, TFRC expression was found to be upregulated in the lung tissues of our experimental PH rat model compared to those of the controls, and the same conclusion was reached in the serum of the PAH patients.
According to our bioinformatics analysis, the observed increase of TFRC in the lung tissue of human PAH patients, as indicated by transcriptomic data, is consistent with the alterations observed in PAH patients and rodent models. These data suggest that TFRC may serve as a potential biomarker for PAH.
肺动脉高压（PAH）是一种危及生命的慢性心肺疾病。然而，目前缺乏研究反映了 PAH 中来自单独基因表达谱的可用生物标志物。
合并 GSE131793 和 GSE113439 数据集进行后续分析，并去除批次效应。然后进行生物信息学分析以识别差异表达基因（DEGs）。使用加权基因共表达网络分析（WGCNA）和蛋白质-蛋白质相互作用（PPI）网络分析进一步筛选枢纽基因。使用基因本体论（GO）、疾病本体论（DO）、京都基因与基因组百科全书（KEGG）和基因集富集分析（GSEA）对交集基因进行功能富集分析。还在验证数据集 GSE53408 和 GSE22356 中分析了肺动脉高压（PAH）患者中枢纽基因表达的表达水平和诊断价值。此外，还在单硝酸异山梨酯（MCT）诱导的肺动脉高压（PH）大鼠模型的肺组织和 PAH 患者的血清中验证了靶基因的表达。
共鉴定出 914 个差异表达基因（DEGs），其中 722 个上调，192 个下调。使用 WGCNA 选择与 PAH 相关的关键模块。通过结合 DEGs 和 WGCNA 的关键模块，选择了 807 个基因。此外，蛋白质-蛋白质相互作用（PPI）网络分析鉴定 HSP90AA1、CD8A、HIF1A、CXCL8、EPRS1、POLR2B、TFRC 和 PTGS2 为枢纽基因。GSE53408 和 GSE22356 数据集用于评估 TFRC 的表达，结果显示其具有稳健的诊断价值。根据 GSEA 富集分析，PAH 相关的生物学功能和途径在 TFRC 水平较高的患者中富集。此外，与对照组相比，我们的实验性 PH 大鼠模型的肺组织中发现 TFRC 表达上调，PAH 患者的血清中也得出了相同的结论。
根据我们的生物信息学分析，从转录组数据中观察到人类 PAH 患者肺组织中 TFRC 的增加与 PAH 患者和啮齿动物模型中观察到的改变一致。这些数据表明 TFRC 可能是 PAH 的潜在生物标志物。
