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脓毒症中多个基因表达谱的生物信息学分析。

Bioinformatics Analysis for Multiple Gene Expression Profiles in Sepsis.

机构信息

Department of Emergency, Tianjin Medical University General Hospital, Tianjin, China (mainland).

出版信息

Med Sci Monit. 2020 Apr 13;26:e920818. doi: 10.12659/MSM.920818.

Abstract

BACKGROUND This work aimed to screen key biomarkers related to sepsis progression by bioinformatics analyses. MATERIAL AND METHODS The microarray datasets of blood and neutrophils from patients with sepsis or septic shock were downloaded from Gene Expression Omnibus database. Then, differentially expressed genes (DEGs) from 4 groups (sepsis versus normal blood samples; septic shock versus normal blood samples; sepsis neutrophils versus normal controls and septic shock neutrophils versus controls) were respectively identified followed by functional analyses. Subsequently, protein-protein network was constructed, and key functional sub-modules were extracted. Finally, receiver operating characteristic analysis was conducted to evaluate diagnostic values of key genes. RESULTS There were 2082 DEGs between blood samples of sepsis patients and controls, 2079 DEGs between blood samples of septic shock patients and healthy individuals, 6590 DEGs between neutrophils from sepsis and controls, and 1056 DEGs between neutrophils from septic shock patients and normal controls. Functional analysis showed that numerous DEGs were significantly enriched in ribosome-related pathway, cell cycle, and neutrophil activation involved in immune response. In addition, TRIM25 and MYC acted as hub genes in protein-protein interaction (PPI) analyses of DEGs from microarray datasets of blood samples. Moreover, MYC (AUC=0.912) and TRIM25 (AUC=0.843) had great diagnostic values for discriminating septic shock blood samples and normal controls. RNF4 was a hub gene from PPI analyses based on datasets from neutrophils and RNF4 (AUC=0.909) was capable of distinguishing neutrophil samples from septic shock samples and controls. CONCLUSIONS Our findings identified several key genes and pathways related to sepsis development.

摘要

背景

本研究旨在通过生物信息学分析筛选与脓毒症进展相关的关键生物标志物。

材料与方法

从基因表达综合数据库中下载脓毒症或感染性休克患者的血液和中性粒细胞的微阵列数据集。然后,分别鉴定 4 组(脓毒症与正常血液样本;感染性休克与正常血液样本;脓毒症中性粒细胞与正常对照;感染性休克中性粒细胞与对照)的差异表达基因(DEGs),并进行功能分析。随后,构建蛋白质-蛋白质网络,并提取关键功能子模块。最后,进行受试者工作特征分析,以评估关键基因的诊断价值。

结果

脓毒症患者与对照组血液样本之间有 2082 个 DEGs,感染性休克患者与健康个体血液样本之间有 2079 个 DEGs,脓毒症与对照组中性粒细胞之间有 6590 个 DEGs,感染性休克患者与正常对照组中性粒细胞之间有 1056 个 DEGs。功能分析表明,大量 DEGs 显著富集在核糖体相关途径、细胞周期和中性粒细胞激活的免疫反应途径中。此外,TRIM25 和 MYC 在血液样本微阵列数据集的 DEGs 蛋白质-蛋白质相互作用(PPI)分析中作为枢纽基因。此外,MYC(AUC=0.912)和 TRIM25(AUC=0.843)对区分感染性休克血液样本和正常对照具有很好的诊断价值。RNF4 是基于中性粒细胞数据集的 PPI 分析中的枢纽基因,RNF4(AUC=0.909)能够区分感染性休克样本和中性粒细胞样本。

结论

本研究确定了一些与脓毒症发展相关的关键基因和途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3ac4/7171431/05f76871ceb3/medscimonit-26-e920818-g001.jpg

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