Department of Emergency, Xijing Hospital, Air Force Medical University, Xi'an 710032, Shaanxi, China.
Genet Res (Camb). 2022 Oct 15;2022:1493744. doi: 10.1155/2022/1493744. eCollection 2022.
Sepsis is a severe disease with high mortality, and liver injury is an independent risk factor for sepsis morbidity and mortality. We analyzed co-differentially expressed genes (co-DEGs) to explore potential biomarkers and therapeutic targets for sepsis-related liver injury. Three gene expression datasets (GSE60088, GSE23767, and GSE71530) were downloaded from the Gene Expression Omnibus (GEO). DEGs were screened between sepsis and control samples using GEO2R. The association of these DEGs with infection and liver disease was analyzed by using the CTD database. GO functional analysis, KEGG pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate the potential molecular mechanism of DEGs. DEGs of different tissues in GSE60088 were analyzed again to obtain specific markers of septic liver injury. Mouse model of sepsis was also established by cecal ligation and puncture (CLP), and the expression of specific markers in liver, lung, and kidney tissues was analyzed using Western blot. Here, we identified 21 DEGs in three datasets with 8 hub genes, all of which showed higher inference scores in liver diseases than bacterial infections. Among them, only TNFRSF1A had a liver-specific differential expression. TNFRSF1A was also confirmed to be specifically reduced in septic liver tissues in mice. Therefore, TNFRSF1A may serve as a potential biomarker for septic liver injury.
脓毒症是一种死亡率很高的严重疾病,肝损伤是脓毒症发病率和死亡率的独立危险因素。我们分析了差异共表达基因(co-DEGs),以探索脓毒症相关肝损伤的潜在生物标志物和治疗靶点。从基因表达综合数据库(GEO)中下载了三个基因表达数据集(GSE60088、GSE23767 和 GSE71530)。使用 GEO2R 在脓毒症和对照样本之间筛选差异表达基因(DEGs)。使用 CTD 数据库分析这些 DEGs 与感染和肝病的关联。进行 GO 功能分析、KEGG 通路富集分析和蛋白质-蛋白质相互作用(PPI)网络分析,以阐明 DEGs 的潜在分子机制。再次分析 GSE60088 中不同组织的 DEGs,以获得脓毒性肝损伤的特异性标志物。还通过盲肠结扎和穿刺(CLP)建立了脓毒症小鼠模型,并使用 Western blot 分析肝脏、肺和肾脏组织中特异性标志物的表达。在这里,我们在三个数据集中共鉴定出 21 个 DEGs,其中有 8 个枢纽基因,所有这些基因在肝病中的推断评分均高于细菌感染。其中,只有 TNFRSF1A 在肝脏中具有特异性差异表达。TNFRSF1A 在脓毒症小鼠肝脏组织中也被证实特异性降低。因此,TNFRSF1A 可能作为脓毒性肝损伤的潜在生物标志物。