小儿脓毒性休克潜在核心基因的鉴定和验证。
Identification and Verification of Potential Core Genes in Pediatric Septic Shock.
机构信息
The Institute of Translational Medicine, The National Engineering Research Center for Bioengineering Drugs and the Technologies, Nanchang University, Nanchang, Jiangxi 330031, China.
The Queen Mary School, Nanchang University, Nanchang, Jiangxi 330031, China.
出版信息
Comb Chem High Throughput Screen. 2022;25(13):2228-2239. doi: 10.2174/1386207325666220310110902.
BACKGROUND
Septic shock is a frequent and costly problem among patients in the pediatric intensive care unit (PICU) and is associated with high mortality and devastating survivor morbidity. In this study, we aimed to screen candidate biomarkers and potential therapeutic targets for septic shock.
METHODS
GSE26440 dataset was downloaded from Gene Expression Omnibus (GEO), including 32 normal controls and 98 children with septic shock RNA samples from whole blood. The pathways and functional annotations of differentially expressed genes (DEGs) in the two types of samples were examined by GO and KEGG pathway enrichment analyses using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Protein-protein interactions (PPI) of the above-described DEGs were investigated using the Search Tool for the Retrieval of Interacting Genes (STRING) and Hub gene identification was performed by the plug-in cytoHubba in Cytoscape software.
RESULTS
A total of 140 genes were identified as DEGs, of which 98 genes were up-regulated and 42 genes were down-regulated. GO function analysis showed that DEGs were significantly enriched in biological processes, including immune response, leukocyte activation involved in immune response, and so on. The top hub genes, namely MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, S100A12, GPR97, and TRAT1 were recognized from the protein-protein interaction (PPI) network. Furthermore, qRT-PCR results demonstrated that the mRNA level of MMP9, CEACAM8, ARG1, MCEMP1, LCN2, RETN, and S100A12 was elevated while GPR97 was decreased in involved mouse and human models. However, TRAT1 expression is species-dependent which was decreased in the mouse septic shock model but elevated in the human LPS-treated macrophages model.
CONCLUSION
Taken together, the identification and validation of several novel hub genes, especially GPR97 and TRAT1, deepen our comprehension of the molecular mechanisms of septic shock progression. These genes may be therapeutic molecular targets or diagnostic biomarkers in patients with septic shock.
背景
脓毒性休克是儿科重症监护病房（PICU）患者中常见且代价高昂的问题，与高死亡率和毁灭性的幸存者发病率有关。在这项研究中，我们旨在筛选脓毒性休克的候选生物标志物和潜在治疗靶点。
方法
从基因表达综合数据库（GEO）下载 GSE26440 数据集，包括 32 名正常对照和 98 名来自全血的脓毒性休克 RNA 样本的儿童。使用 DAVID 工具对两种类型样本中的差异表达基因（DEGs）进行 GO 和 KEGG 通路富集分析，以检查途径和功能注释。使用 Search Tool for the Retrieval of Interacting Genes（STRING）研究上述 DEGs 的蛋白质-蛋白质相互作用（PPI），并使用 Cytoscape 软件中的插件 cytoHubba 进行 Hub 基因鉴定。
结果
共鉴定出 140 个 DEG，其中 98 个基因上调，42 个基因下调。GO 功能分析表明，DEGs 显著富集于生物学过程，包括免疫反应、白细胞激活参与免疫反应等。从蛋白质-蛋白质相互作用（PPI）网络中识别出顶级 Hub 基因，即 MMP9、CEACAM8、ARG1、MCEMP1、LCN2、RETN、S100A12、GPR97 和 TRAT1。此外，qRT-PCR 结果表明，在涉及的小鼠和人类模型中，MMP9、CEACAM8、ARG1、MCEMP1、LCN2、RETN 和 S100A12 的 mRNA 水平升高，而 GPR97 降低。然而，TRAT1 的表达具有物种依赖性，在小鼠脓毒性休克模型中降低，而在人类 LPS 处理的巨噬细胞模型中升高。
结论
综上所述，几个新的 Hub 基因，特别是 GPR97 和 TRAT1 的鉴定和验证，加深了我们对脓毒性休克进展的分子机制的理解。这些基因可能是脓毒性休克患者的治疗分子靶点或诊断生物标志物。
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