高原肺水肿新型生物标记物的研究

Research on Novel Biomarkers of High Altitude Pulmonary Edema

目的研究高原肺水肿的发生和早期进展潜在生物标志物,进一步为高海拔肺水肿的发病和早期进展机制提供理论基础。方法从GEO数据库中提取出人类基因表达谱GSE52209,使用R软件在数据集中筛选急进入高原48~72 h内高原适应组和高原肺水肿组的差异表达基因(DEGs),通过GO和KEGG探究高原肺水肿的发生和早期进展机制,利用cytoscape软件的MCC算法鉴定枢纽基因,利用Lasso-Cox回归分析和ROC曲线分析预测和验证诊断标记物,利用R软件检测数据集枢纽基因的相对表达水平,利用networkanalyst和cytoscape软件鉴定与枢纽基因作用的miRNA和枢纽miRNA。结果共鉴定出DEGs 216个,其中196个基因表达上调,20个基因表达下调;GO和KEGG分析结果显示,DEGs主要与代谢异常和氧化应激相关;共筛选出7个高原肺水肿诊断标记物(ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L、SEC61A1),结合gene-miRNA网络,hsa-miR-335-5p、hsa-miR-16-5p、hsa-miR-149-5p和hsa-miR-615-3p可能是高原肺水肿发生和早期进展相关的枢纽miRNA。结论ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L、SEC61A1、hsa-miR-335-5p、hsa-miR-16-5p、hsa-miR-149-5p和hsa-miR-615-3p可能是高原肺水肿发病和早期进展的重要生物标记物,其中ARRB2、RPLP0、JAK2、ICAM1、ESPL1、RAD54L和SEC61A1可能是高原肺水肿的早期诊断标记物。

Objective To study the potential biomarkers of the occurrence and early progression of high altitude pulmonary edema,and to further provide a theoretical basis for the pathogenesis and early progression of high altitude pulmonary edema.Methods The human gene expression profile GSE52209 was extracted from the GEO database.R software was used to screen differentially expressed genes(DEGs)between the high-altitude adaptation group and the high-altitude pulmonary edema group within 48-72 h after rapid entry into the plateau in the data set.GO and KEGG were used to explore the mechanism of the occurrence and early progression of high-altitude pulmonary edema.The MCC algorithm of cytoscape software was used to identify hub genes.Lasso-Cox regression analysis and ROC curve analysis were used to predict and verify diagnostic markers.R software was used to detect the relative expression level of hub genes in the data set.Networkanalyst and cytoscape software were used to identify miRNAs and hub miRNAs that interact with hub genes.Results A total of 216 DEGs were identified,of which 196 genes were up-regulated and 20 genes were down-regulated.GO and KEGG analysis showed that DEGs were mainly related to metabolic abnormalities and oxidative stress.A total of 7 diagnostic markers of high altitude pulmonary edema(ARRB2,RPLP0,JAK2,ICAM1,ESPL1,RAD54L,SEC61A1)were screened out.Combined with gene-miRNA network,hsa-miR-335-5p,hsa-miR-16-5p,hsa-miR-149-5p and hsa-miR-615-3p may be hub miRNAs related to the occurrence and early progression of high altitude pulmonary edema.Conclusion ARRB2,RPLP0,JAK2,ICAM1,ESPL1,RAD54L,SEC61A1,hsa-miR-335-5p,hsa-miR-16-5p,hsa-miR-149-5p and hsa-miR-615-3p may be important biomarkers for the pathogenesis and early progression of high altitude pulmonary edema.ARRB2,RPLP0,JAK2,ICAM1,ESPL1,RAD54L and SEC61A1 may be early diagnostic markers for high altitude pulmonary edema.