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脓毒症诱导的多器官功能衰竭基因表达谱的综合分析确定了其有价值的生物标志物。

Comprehensive Analysis of Gene Expression Profiles of Sepsis-Induced Multiorgan Failure Identified Its Valuable Biomarkers.

作者信息

Wang Yumei, Yin Xiaoling, Yang Fang

机构信息

Department of Critical Care Medicine, Weihai Central Hospital , Weihai, China .

出版信息

DNA Cell Biol. 2018 Feb;37(2):90-98. doi: 10.1089/dna.2017.3944. Epub 2017 Dec 18.

Abstract

Sepsis is an inflammatory-related disease, and severe sepsis would induce multiorgan dysfunction, which is the most common cause of death of patients in noncoronary intensive care units. Progression of novel therapeutic strategies has proven to be of little impact on the mortality of severe sepsis, and unfortunately, its mechanisms still remain poorly understood. In this study, we analyzed gene expression profiles of severe sepsis with failure of lung, kidney, and liver for the identification of potential biomarkers. We first downloaded the gene expression profiles from the Gene Expression Omnibus and performed preprocessing of raw microarray data sets and identification of differential expression genes (DEGs) through the R programming software; then, significantly enriched functions of DEGs in lung, kidney, and liver failure sepsis samples were obtained from the Database for Annotation, Visualization, and Integrated Discovery; finally, protein-protein interaction network was constructed for DEGs based on the STRING database, and network modules were also obtained through the MCODE cluster method. As a result, lung failure sepsis has the highest number of DEGs of 859, whereas the number of DEGs in kidney and liver failure sepsis samples is 178 and 175, respectively. In addition, 17 overlaps were obtained among the three lists of DEGs. Biological processes related to immune and inflammatory response were found to be significantly enriched in DEGs. Network and module analysis identified four gene clusters in which all or most of genes were upregulated. The expression changes of Icam1 and Socs3 were further validated through quantitative PCR analysis. This study should shed light on the development of sepsis and provide potential therapeutic targets for sepsis-induced multiorgan failure.

摘要

脓毒症是一种与炎症相关的疾病,严重脓毒症会导致多器官功能障碍,这是非冠心病重症监护病房患者最常见的死亡原因。新治疗策略的进展已证明对严重脓毒症的死亡率影响甚微,不幸的是,其机制仍知之甚少。在本研究中,我们分析了伴有肺、肾和肝功能衰竭的严重脓毒症的基因表达谱,以鉴定潜在的生物标志物。我们首先从基因表达综合数据库下载基因表达谱,对原始微阵列数据集进行预处理,并通过R编程软件鉴定差异表达基因(DEG);然后,从注释、可视化和综合发现数据库中获得肺、肾和肝功能衰竭脓毒症样本中DEG的显著富集功能;最后,基于STRING数据库构建DEG的蛋白质-蛋白质相互作用网络,并通过MCODE聚类方法获得网络模块。结果,肺功能衰竭脓毒症的DEG数量最多,为859个,而肾功能和肝功能衰竭脓毒症样本中的DEG数量分别为178个和175个。此外,在三个DEG列表中获得了17个重叠项。发现与免疫和炎症反应相关的生物学过程在DEG中显著富集。网络和模块分析确定了四个基因簇,其中所有或大多数基因均上调。通过定量PCR分析进一步验证了Icam1和Socs3的表达变化。本研究应有助于阐明脓毒症的发展,并为脓毒症诱导的多器官衰竭提供潜在的治疗靶点。

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