Fang Xiao, Duan Shu-Fang, Gong Yu-Zhou, Wang Fei, Chen Xu-Lin
Department of Burns, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People's Republic of China.
J Inflamm Res. 2020 Dec 1;13:1029-1041. doi: 10.2147/JIR.S282722. eCollection 2020.
Patients with severe burns continue to display a high mortality rate during the initial shock period. The precise molecular mechanism underlying the change in host response during severe burn shock remains unknown. This study aimed to identify key genes leading to the change in host response during burn shock.
The GSE77791 dataset, which was utilized in a previous study that compared hydrocortisone administration to placebo (NaCl 0.9%) in the inflammatory reaction of severe burn shock, was downloaded from the Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed genes (DEGs). Functional enrichment analyses of Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were performed. The protein-protein interaction (PPI) network of DEGs was constructed using the Search Tool for the Retrieval of Interacting Genes (STRING) database and then visualized in Cytoscape. In addition, important modules in this network were selected using the Molecular Complex Detection (MCODE) algorithm, and hub genes were identified in cytoHubba, a Cytoscape plugin.
A total of 1059 DEGs (508 downregulated genes and 551 upregulated genes) were identified from the dataset. The DEGs enriched in GO terms and KEGG pathways were related to immune response. The PPI network contained 439 nodes and 2430 protein pairs. Finally, important modules and hub genes were identified using the different Cytoscape plugins. The key genes in burn shock were identified as arginase 1 (), cytoskeleton-associated protein (), complement C3a receptor (), neutrophil elastase (), gamma-glutamyl hydrolase (), orosomucoid (), and quiescin sulfhydryl ().
The DEGs, functional terms and pathways, and hub genes identified in the present study can help shed light on the molecular mechanism underlying the changes in host response during burn shock and provide potential targets for early detection and treatment of burn shock.
严重烧伤患者在初始休克期死亡率仍居高不下。严重烧伤休克期间宿主反应变化的精确分子机制尚不清楚。本研究旨在鉴定导致烧伤休克期间宿主反应变化的关键基因。
从基因表达综合数据库（GEO）下载先前一项研究中使用的GSE77791数据集，该研究比较了氢化可的松与安慰剂（0.9%氯化钠）在严重烧伤休克炎症反应中的作用，并进行分析以鉴定差异表达基因（DEG）。对基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路进行功能富集分析。使用检索相互作用基因的搜索工具（STRING）数据库构建DEG的蛋白质-蛋白质相互作用（PPI）网络，然后在Cytoscape中进行可视化。此外，使用分子复合物检测（MCODE）算法选择该网络中的重要模块，并在Cytoscape插件cytoHubba中鉴定枢纽基因。
从数据集中鉴定出总共1059个DEG（508个下调基因和551个上调基因）。在GO术语和KEGG通路中富集的DEG与免疫反应有关。PPI网络包含439个节点和2430个蛋白质对。最后，使用不同的Cytoscape插件鉴定了重要模块和枢纽基因。烧伤休克中的关键基因被鉴定为精氨酸酶1、细胞骨架相关蛋白、补体C3a受体、中性粒细胞弹性蛋白酶、γ-谷氨酰水解酶、类粘蛋白和巯基喹啉。
本研究中鉴定的DEG、功能术语和通路以及枢纽基因有助于阐明烧伤休克期间宿主反应变化的分子机制，并为烧伤休克的早期检测和治疗提供潜在靶点。
