基于GEO数据库芯片的脓毒症关键基因筛选与生物信息学分析

Screening and bioinformatics analysis of key genes for sepsis based on GEO database microarray

目的对脓毒症患者基因芯片数据进行生物信息学分析,寻找差异基因谱。方法从基因综合表达数据库中筛选出脓毒症高通量基因芯片GSE28750、GSE57065、GSE95233,通过GEO2R筛选出脓毒症患者与健康志愿者的差异基因,对差异基因进行基因本体论功能注释和京都基因与基因组百科全书通路分析,并进行蛋白质相互作用网络可视化分析,利用Cytoscape软件中Cytohubba和MCODE插件寻找关键基因。结果共筛选出275个表达差异基因,主要分布于细胞膜、细胞质膜和细胞外间隙,主要参与免疫反应、固有免疫应答、炎症反应等生物学过程,富集于T细胞受体信号通路、造血细胞系、细胞黏附分子等通路。最后筛选出10个关键基因,分别为白细胞分化抗原(CD)4、CD8A、C-C趋化因子配体5(CCL5)、淋巴细胞特异蛋白酪氨酸激酶(LCK)、CD28、CD2、白介素7受体(IL-7R)、CD3E、白介素2受体β亚基(IL-2Rβ)、穿孔素(PRF)1。结论CD4、CD8A、CCL5、LCK、CD28、CD2、IL-7R、CD3E、IL-2Rβ、PRF1是脓毒症关键基因,可能与脓毒症发生、发展相关。

Objective To perform bioinformatics analysis on the gene microarray data of septic patients and find the differential gene expression profile.Methods Sepsis high-throughput gene chips GSE28750,GSE57065 and GSE95233 were screened from GEO database.The differential genes between sepsis group and healthy control group were screened by GEO2R.Gene ontology and Kyoto Gene and Genome Encyclopedia pathway enrichment analyses were perfomed for differential genes,and the protein interaction network was visualized.Cytohubba and MCODE in Cytoscape software were used to find the key genes.Results A total of 275 differentially expressed genes were screened,which were mainly distributed in cell membrane,cytoplasmic membrane and extracellular gaps.They were mainly involved in biological functions such as immune response,innate immune response and inflammatory response,and enriched in T cell receptor signaling pathway,hematopoietic cell lineage and cell adhesion molecule.Finally,ten key genes were screened,namely leukocyte differentiation antigen CD4,CD8A,chemokine C-C motif ligard 5(CCL5),lymphocyte-specific protein tyrosine kinase(LCK),CD28,CD2,interleukin 7 receptor(IL-7R),CD3E,interleukin 2 receptor beta(IL-2Rβ)and perforin(PRF)1.Conclusion CD4,CD8A,CCL5,LCK,CD28,CD2,IL-7R,CD3E,IL-2Rβand PRF1 were key genes for sepsis,which may be related to the occurrence and progression of sepsis.