目的 通过公共数据库筛选急性肺损伤（ALI）及急性呼吸窘迫综合征（ARDS）相关分子标志物,并探索其临床意义。方法 利用基因表达综合数据库（GEO）中有关ALI/ARDS基因表达芯片研究的两个数据集GSE76293和GSE10474,通过STRING网站和Cytoscape软件对差异基因进行蛋白互作网络分析并筛选ALI/ARDS相关关键基因。采用A549细胞构建ALI模型,并通过转录组测序验证关键基因在细胞中的表达差异情况。结果 2个GEO数据集中共筛选出共同上调基因27个,共同下调基因26个。主要参与抗原加工和外源抗原递呈、免疫受体活性调节、内质网膜构成等生物学功能,且与抗原加工、细胞分化等信号通路有关。蛋白互作网络分析共筛选出10个ALI/ARDS相关关键基因,分别为CD4、HLA-DQB1、CD74、HLA-DRA、FCGR2B、TOR1A、RELA、NME8、RNF19B、RHOB。细胞转录组测序结果显示,关键基因的上调或下调特征及表达差异情况与GEO数据集分析结果一致。结论 CD4等关键基因可能参与ALI/ARDS发生、发展的生物学过程,是ALI/ARDS临床诊断及预后预测的潜在个体化分子标志物。

Objective To identify molecular biomarkers associated with acute lung injury（ALI）/ acute respiratory distress syndrome（ARDS）and to explore their clinical significance with public databases. Methods Two datasets GSE76293 and GSE10474 in Gene Expression Omnibus（GEO）database for ALI/ARDS gene expression chip study were used to screen genes with significant differences in both datasets．The protein-protein interaction（PPI）analysis of co-expression genes was performed based on the STRING website and Cytoscape software,and then key genes related to ALI/ARDS were identified with cytoHubba method．The ALI model was constructed using A549 cells cultured in vitro,and the expression differences of key genes in the cells were verified by RNA sequencing. Results A total of 27 up-regulated genes and 26 down-regulated genes were screened in both the two GEO datasets with Venn Diagramm．These co-expression genes were mainly involved in biological functions such as antigen processing and presentation of exogenous peptide antigen,immune receptor activity,integral component of lumenal side of endoplasmic reticulum membrane and were related to signal pathways such as antigen processing and cell differentiation．A total of 10 key genes（CD4,HLA-DQB1,CD74,HLA-DRA,FCGR2B,TOR1A,RELA,NME8,RNF19B,RHOB）related to ALI/ARDS were identified． The results of cell RNA sequencing showed that the up-regulated or down-regulated characteristics and expression differences of key genes were consistent with the results of GEO datasets. Conclusions Several key genes identified in this study may be involved in the biological process of ALI/ARDS development,and may be potential individualized molecular markers for clinical diagnosis and prognosis prediction of ALI/ARDS．