Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification

IF 4.7 2区医学 Q1 RESPIRATORY SYSTEM

Respiratory Research Pub Date : 2024-08-03 DOI:10.1186/s12931-024-02928-6

Chuang Yang, Yi-Hang Liu, Hai-Kuo Zheng

{"title":"Identification of TFRC as a biomarker for pulmonary arterial hypertension based on bioinformatics and experimental verification","authors":"Chuang Yang, Yi-Hang Liu, Hai-Kuo Zheng","doi":"10.1186/s12931-024-02928-6","DOIUrl":null,"url":null,"abstract":"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.","PeriodicalId":21109,"journal":{"name":"Respiratory Research","volume":"34 1","pages":""},"PeriodicalIF":4.7000,"publicationDate":"2024-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12931-024-02928-6","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"RESPIRATORY SYSTEM","Score":null,"Total":0}

引用次数: 0

Abstract

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.

查看原文本刊更多论文

基于生物信息学和实验验证鉴定肺动脉高压的生物标记物 TFRC

肺动脉高压（PAH）是一种危及生命的慢性心肺疾病。然而，很少有研究能从 PAH 的独立基因表达谱中反映出可用的生物标志物。为了进行后续分析，我们合并了 GSE131793 和 GSE113439 数据集，并剔除了批次效应。然后进行生物信息学分析，以确定差异表达基因（DEGs）。然后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出中心基因。利用基因本体（GO）、疾病本体（DO）、京都基因与基因组百科全书（KEGG）和基因组富集分析（GSEA）对交叉基因进行了功能富集分析。在验证数据集 GSE53408 和 GSE22356 中，还分析了肺动脉高压（PAH）患者中枢基因的表达水平和诊断价值。此外，还验证了单克隆肾上腺素（MCT）诱导的肺动脉高压（PH）大鼠模型肺部和 PAH 患者血清中靶基因的表达。共鉴定出 914 个差异表达基因（DEG），其中上调基因 722 个，下调基因 192 个。利用 WGCNA 筛选出了与 PAH 相关的关键模块。结合 DEGs 和 WGCNA 的关键模块，筛选出 807 个基因。此外，通过蛋白-蛋白相互作用（PPI）网络分析，确定了 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，也显示了其强大的诊断价值。根据 GSEA 富集分析，TFRC 水平高的患者体内富集了 PAH 相关的生物功能和通路。此外，与对照组相比，我们发现 TFRC 在实验 PH 大鼠肺组织中的表达上调，在 PAH 患者的血清中也得出了同样的结论。根据我们的生物信息学分析，转录组数据显示，在人类 PAH 患者肺组织中观察到的 TFRC 增加与 PAH 患者和啮齿类动物模型中观察到的改变一致。这些数据表明，TFRC 可作为 PAH 的潜在生物标记物。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Respiratory Research 医学-呼吸系统

自引率

1.70%

发文量

314

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.