Zhang Z-L, Wu W-C, Liu J-Q, Yao Y-B, Pan M-D, Yang C-B, Wang J-G, Huang X-W, Lin J-Y
Department of Emergency and Critical Care Medicine, the First Affiliated Hospital of Xiamen University, Xiamen, China.
Eur Rev Med Pharmacol Sci. 2014;18(8):1181-8.
Prognostic blood biomarkers in the setting of acute ischemic stroke have become increasingly relevant for risk stratification, monitoring disease and response to therapies, developing targets for neuroprotective treatment and as surrogate end points for treatment trials.
We aim to find the feature genes which can accurately detect acute ischemic stroke and perform function analysis of these crucial genes in peripheral blood mononuclear cells.
The gene expression profile GSE22255 was downloaded from Gene Expression Omnibus (GEO) database which includes 20 ischemic stroke patients and 20 controls. The differentially expressed genes between patients and controls samples were identified with packages in R language. The selected differentially expressed genes were further analyzed using bioinformatics methods. Software STRING (Search Tool for the Retrieval of Interacting Genes) was used to establish co-expression network. GOTM (General Ocean Turbulence Model) software was used to obtain differentially expressed gene enriched modules. The functions of genes in modules were analyzed by using software GeneCodis.
A total of 37 genes were identified as differentially expressed genes by comparing peripheral blood mononuclear cells gene expression of ischemic stroke patients and 20 controls. A co-expression network was constructed within 30 differentially expressed genes, among which gene interleukin-8 (IL-8) and tumor necrosis factor (TNF) showed the highest node degree. Genes in the module containing IL-8 and TNF were significantly enriched in 6 biological functions, and the most significant function was respond to stimulation.
Our results highlight that genes IL-8 and TNF have close relationship with acute ischemic stroke, and the expression patterns of these genes may be valid targets for new medications able to modify the ischemic stroke process.
急性缺血性卒中环境下的预后血液生物标志物在风险分层、监测疾病及对治疗的反应、开发神经保护治疗靶点以及作为治疗试验的替代终点方面变得越来越重要。
我们旨在寻找能够准确检测急性缺血性卒中的特征基因,并对这些关键基因在外周血单个核细胞中的功能进行分析。
从基因表达综合数据库(GEO)下载基因表达谱GSE22255,其中包括20例缺血性卒中患者和20例对照。使用R语言中的软件包识别患者和对照样本之间的差异表达基因。对选定的差异表达基因进一步采用生物信息学方法进行分析。使用STRING(搜索相互作用基因的工具)软件建立共表达网络。使用GOTM(通用海洋湍流模型)软件获得差异表达基因富集模块。通过GeneCodis软件分析模块中基因的功能。
通过比较缺血性卒中患者和20例对照的外周血单个核细胞基因表达,共鉴定出37个差异表达基因。在30个差异表达基因中构建了一个共表达网络,其中白细胞介素-8(IL-8)基因和肿瘤坏死因子(TNF)显示出最高的节点度。包含IL-8和TNF的模块中的基因在6种生物学功能中显著富集,最显著的功能是对刺激的反应。
我们的结果突出表明,IL-8和TNF基因与急性缺血性卒中有密切关系,这些基因的表达模式可能是能够改变缺血性卒中进程的新药物的有效靶点。