脓毒血症患者急性肺损伤的差异基因表达分析  

Differential gene expression analysis of acute lung injury in patients with sepsis

作　　者：余彪 闫志国[2] 干尧鳘 Yu Biao;Yan Zhiguo;Gan Yaofu(Department of Emergency,Meishan People′s Hospital,Meishan Hospital,West China Hospital,Sichuan University,Meishan 620010,China;Department of Thoracic Surgery,Kunming First People′s Hospital,Kunming 650011,China)

机构地区：[1]四川大学华西医院眉山医院眉山市人民医院急诊科,620010 [2]昆明市第一人民医院胸外科,650011

出　　处：《国际呼吸杂志》2020年第18期1374-1380,共7页International Journal of Respiration

摘　　要：目的借助生物信息学分析脓毒血症患者急性肺损伤(ALI)的差异基因,为临床的进一步研究提供理论支持。方法首先下载基因芯片数据集GSE10474,并使用limma包对数据进行了标准化处理,接着利用贝叶斯算法筛选脓毒血症和ALI的差异靶点基因并对其结果进行可视化处理,之后利用R的ClusterProfile包对所筛选出的差异基因进行功能注释(GO)和通路分析(KEGG),最后借助string数据库和cytoscape软件对差异基因进行蛋白互作网络分析并构建及识别网络中的核心驱动基因。结果脓毒血症合并ALI组(n=13)和单纯脓毒血症组(n=21)数据经标准化处理前,其基线较为紊乱,而在进行标准化处理后,基线基本趋于一致。初步筛选出73个差异基因(45个上调基因和28个下调基因)。前10个差异基因中,上调基因为BTNL8、CDKN1A、TREM1、TAK1、H4FH,下调基因为CYBRD1、HOPX、UPB1、NME8、FAR2;且前10个差异基因在脓毒血症患者和脓毒血症合并ALI患者中的表达差异有统计学意义。GO富集分析可见这些差异基因主要富集在反式高尔基网络膜、细胞膜腔侧以及IRE1介导的未折叠蛋白反应中。KEGG分析其通路信号有3条,即ZAP-70酪氨酸激酶、CD3和TCR Zeta链的磷酸化以及PD-1信号通路。string数据库和cytoscape软件分析发现FCGR2B、HLA-DQB1、HLA-DRA、CD74、CD86、CD4、SEC31A与其他基因存在较强的互作关系。结论应用生物信息学可有效分析脓毒血症患者合并ALI的差异基因,为研究脓毒血症的发病机制提供一定方向。Objective To analyze the differential genes of acute lung injury(ALI)in patients with sepsis by using bioinformatics to provide theoretical support for further clinical researches.Methods The gene chip data set GSE10474 was downloaded,and the limma package was used to standardize the data.Bayesian algorithm was used to screen the differential target genes of sepsis and ALI and visualize the results.Then,R ClusterProfile package was used to perform functional annotation(GO)and pathway analysis(KEGG)on the selected differential factors.Finally,the string database and cytoscape software was used to analyze the protein interaction network of the differential genes and construct and identify the core driver gene in the network.Results Before the data of two groups were standardized,their baselines were disordered,and after normalization,the baselines were basically consistent.73 differential genes were initially screened(45 up-regulated genes and 28 down-regulated genes).Among the top ten differential genes,the up-regulated genes were BTNL8,CDKN1A,TREM1,TAK1,H4FH,and the down-regulated genes were CYBRD1,HOPX,UPB1,NME8,and FAR2.The expressions of the top ten differential genes in sepsis patients and sepsis patients with ALI were significantly different.GO enrichment analysis showed that these differential genes were mainly concentrated in the trans-Golgi network membrane,the cell membrane cavity side and the IRE1-mediated unfolded protein response.KEGG analysis showed three pathway signals,including ZAP-70 tyrosine kinase,CD3 and TCR Zeta chain phosphorylation and PD-1 signaling.The string database and cytoscape software analysis found that FCGR2B,HLA-DQB1,HLA-DRA,CD74,CD86,CD4,SEC31A and other genes had strong interactions.Conclusions The application of bioinformatics can effectively analyze the differential genes of sepsis patients combined with ALI,and provide a certain direction for studying the pathogenesis of sepsis.

关 键 词：脓毒血症 急性肺损伤 差异基因 生物信息学 

分 类 号：R459.7[医药卫生—急诊医学]