脓毒症关键基因的筛选与生物信息学分析

Screening of key genes in sepsis based on bioinformatics

摘要:

目的 利用生物信息学研究脓毒症的潜在关键基因。 方法 从基因表达数据库GEO中下载脓毒症基因表达数据集GSE28750：包括10名脓毒症患者为实验组，20名正常人为对照组。通过GEO2R软件数据进行均一化处理以及差异基因筛选（P < 0.01，倍数> 2倍）。差异基因被提交到DAVID进行GO分析和Pathway分析，再将筛选的差异基因提交到STRING中构建蛋白-蛋白互作（PPI）网络寻找关键基因。最后，通过GraphPad Prism 7做筛选关键基因的生存曲线，进而预测关键基因对脓毒血症预后的影响。 结果 295个差异基因被筛选出来，包括188个基因上调和107个基因下调。差异基因主要富集的GO是免疫反应，小分子代谢过程，信号转导等；激活的信号通路包括：代谢途径，T细胞受体信号通路，MAPK信号通路等。PPI网络显示出关键基因CD247，LCK位于网络核心，且CD247，LCK高表达组生存率越高（P < 0.05）。 结论 关键基因CD247，LCK与脓毒症患者生存率呈正相关，可能会成为新的脓毒症生物标志物或药物靶标，但其具体功能还需进一步研究证实。

Abstract:

Objective To investigate the potential key genes in sepsis using bioinformatics. Methods The sepsis-related gene expression data set GSE28750 was downloaded from the Gene Expression Omnibus，including 10 patients with sepsis as the experimental group and 20 healthy people as the control group. Data homogenization and differential gene screening were performed by GEO2R software （P < 0.01，fold change > 2 times）. The differentially expressed genes （DEGs） were submitted to DAVID for GO analysis and Pathway analysis，and then the identified DEGs were submitted to STRING to construct a protein-protein interaction （PPI） network to search for key genes. The survival curves of the identified key genes were plotted by GraphPad Prism 7.0 to predict the impact of key genes on the prognosis of sepsis. Results A total of 295 DEGs were screened out，including 188 up-regulated genes and 107 down-regulated genes. The GO where DEGs were enriched mainly contained immune response，small molecule metabolic process，and signal transduction. The activated signaling pathways included metabolic pathway，T cell receptor signaling pathway，and MAPK signaling pathway. The PPI network showed that the key genes CD247 and LCK were located in the core，and that the high expression groups of CD247 and LCK had higher survival rates （P < 0.05）. Conclusion The key genes CD247 and LCK are positively correlated with the survival rate of patients with sepsis. They may become new biomarkers or drug targets for sepsis，but their specific functions need to be confirmed by further studies.