Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling
Genomic biomarkers and cellular pathways of ischemic stroke by RNA gene expression profiling
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DOI：
10.1212/wnl.0b013e3181f2b37f
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发表时间：
2010-09-14
期刊：
影响因子：
9.9
通讯作者：
Matarin, M.
中科院分区：
文献类型：
--
作者：
Barr, T. L.;Conley, Y.;Matarin, M.
目的：本研究的目的是通过基因表达谱分析和通路分析深入了解急性缺血性脑血管综合征（AICS）的分子机制。方法：收集39例MRI诊断的AICS患者和25例年龄>18岁的非卒中对照者的外周全血样本。从稳定在Paxgene RNA管中的全血中提取总RNA，扩增，并与Illumina HumanRef-8v 2珠芯片杂交。在GeneSpring中使用t检验以单变量方式比较中风患者和对照受试者之间的基因表达。在控制年龄、高血压和血脂异常的逻辑回归模型中检测显著基因。通过Bonferroni校正了1型错误的膨胀，并进行了Insurance Systems Pathway分析。采用Taqman基因表达分析技术，通过QRT-PCR进行验证。结果：采用基因表达谱分析技术，在缺血性卒中患者的全血中鉴定出9个基因。这9个基因中的5个在先前发表的中风表达谱研究中被鉴定，因此可能是中风的生物标志物。通路分析显示，Toll样受体信号传导作为一个非常重要的典型途径存在于外周全血中的患者AICS.Conclusions：我们的研究强调了相关的先天免疫系统通过Toll样受体信号传导作为一个调解人的反应缺血性中风，并支持声称基因表达谱可用于识别缺血性中风的生物标志物。需要进一步的研究来验证和完善这些生物标志物的诊断潜力。神经病学（R）2010;75：1009-1014
Objective: The objective of this study was to provide insight into the molecular mechanisms of acute ischemic cerebrovascular syndrome (AICS) through gene expression profiling and pathway analysis.Methods: Peripheral whole blood samples were collected from 39 MRI-diagnosed patients with AICS and 25 nonstroke control subjects >18 years of age. Total RNA was extracted from whole blood stabilized in Paxgene RNA tubes, amplified, and hybridized to Illumina HumanRef-8v2 bead chips. Gene expression was compared in a univariate manner between stroke patients and control subjects using t test in GeneSpring. The significant genes were tested in a logistic regression model controlling for age, hypertension, and dyslipidemia. Inflation of type 1 error was corrected by Bonferroni and Ingenuity Systems Pathway analysis was performed. Validation was performed by QRT-PCR using Taqman gene expression assays.Results: A 9-gene profile was identified in the whole blood of ischemic stroke patients using gene expression profiling. Five of these 9 genes were identified in a previously published expression profiling study of stroke and are therefore likely biomarkers of stroke. Pathway analysis revealed toll-like receptor signaling as a highly significant canonical pathway present in the peripheral whole blood of patients with AICS.Conclusions: Our study highlights the relevance of the innate immune system through toll-like receptor signaling as a mediator of response to ischemic stroke and supports the claim that gene expression profiling can be used to identify biomarkers of ischemic stroke. Further studies are needed to validate and refine these biomarkers for their diagnostic potential. Neurology (R) 2010;75:1009-1014