摘要
目的急性呼吸窘迫综合征(acute respiratory distress syndrome,ARDS)相关肺纤维化(pulmonary fibrosis,PF)目前缺乏应用于临床的诊断生物标志物,本文应用转录组学寻找ARDS中的肺纤维化相关基因并探索ARDS-PF的诊断生物标志物。方法联合分析GEO数据库中ARDS-PF转录组数据集GSE190496和特发性肺纤维化转录组数据集GSE10667获得共有差异表达基因(differentially expressed genes,DEGs),通过基因本体论(Gene Ontology,GO)和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)数据库对DEGs进行功能富集分析、STRING数据库构建DEGs的蛋白质-蛋白质相互作用网络(protein-protein interaction,PPI)、cytoscape软件cytoHubba插件筛选核心基因,在ARDS-PF转录组数据集GSE206788中验证,绘制核心基因的受试者工作特征(receiver operating characteristic,ROC)曲线并计算曲线下面积(area under the curve,AUC)。结果筛选出234个共有DEGs,上调DEGs有132个,下调DEGs有102个。GO和KEGG富集显示这些基因主要参与胶原蛋白生成、细胞外基质胶原沉积、细胞外基质受体互作、局灶黏附、PI3K-Akt通路等生物过程和途径。STRING构建PPI网络并利用cytoscape筛选出的10个核心基因为COL1A1、COL1A2、COL3A1、COL5A2、CXCL12、IGF1、MMP2、SPP1、PTGS2和THBS2,其中9个核心基因在GSE206788中差异表达显著(P<0.05),ROC曲线显示COL1A1、COL1A2、COL3A1、CXCL12、IGF1、SPP1和PTGS2的AUC值≥0.9(P<0.01)。结论COL1A1、COL1A2、COL3A1、CXCL12、IGF1、SPP1和PTGS2可能是潜在的ARDS-PF诊断生物标志物。
Objective Currently,there is a lack of clinically applicable diagnostic biomarkers for pulmonary fibrosis(PF)associated with acute respiratory distress syndrome(ARDS).This study aimed to identify PF-related genes in ARDS through transcriptomic analysis and explore potential diagnostic biomarkers for ARDS-associated pulmonary fibrosis(ARDS-PF).Methods Transcriptomic datasets GSE190496(ARDS-PF)and GSE10667(idiopathic pulmonary fibrosis)were jointly analyzed from the GEO database to identify common differentially expressed genes(DEGs).Gene Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were performed to investigate the functions of DEGs.A protein-protein interaction(PPI)network was constructed using the STRING database,and key hub genes were identified with the cytoHubba plugin in Cytoscape.The identified hub genes were validated in the ARDS-PF transcriptomic dataset GSE206788.Receiver operating characteristic(ROC)curves were generated,and the area under the curve(AUC)was calculated to evaluate the diagnostic performance of the hub genes.Results A total of 234 common DEGs were identified,including 132 upregulated and 102 downregulated genes.GO and KEGG enrichment analyses revealed that these genes were mainly involved in biological processes and pathways such as collagen formation,extracellular matrix(ECM)collagen deposition,ECM-receptor interaction,focal adhesion,and the PI3K-Akt signaling pathway.The PPI network constructed via STRING and analyzed with Cytoscape identified 10 hub genes:COL1A1,COL1A2,COL3A1,COL5A2,CXCL12,IGF1,MMP2,SPP1,PTGS2,and THBS2.Among them,9 hub genes were significantly differentially expressed in GSE206788(P<0.05).ROC curve analysis showed that COL1A1,COL1A2,COL3A1,CXCL12,IGF1,SPP1,and PTGS2 had AUC≥0.9(P<0.01).Conclusion COL1A1,COL1A2,COL3A1,CXCL12,IGF1,SPP1,and PTGS2 may serve as potential diagnostic biomarkers for ARDS-PF.
作者
田学
魏东坡
孟潇潇
谢晖
王瑞兰
Tian Xue;Wei Dongpo;Meng Xiaoxiao;Xie Hui;Wang Ruilan(Department of Critical Care Medicine,Shanghai General Hospital of Nanjing Medical University,Shanghai Jiaotong University,School of Medicine,Shanghai 200080,China)
出处
《中华肺部疾病杂志(电子版)》
2025年第4期534-539,共6页
Chinese Journal of Lung Diseases(Electronic Edition)
基金
国家自然科学基金面上项目(82472218,82072210)
国家临床重点专科建设项目(Z155080000004)
国家重点研发计划(2024YFC30444000)
上海市科委基金资助(23Y31900100)。
关键词
急性呼吸窘迫综合征
肺纤维化
转录组学
生物标志物
Acute respiratory distress syndrome
Pulmonary fibrosis
Transcriptomics
Biomarker
