Department of Clinical Medicine, Affiliated of Southwest Medical University, Luzhou, 646000, China.
Department of Pediatrics, People\'s Hospital of Lushan County, Ya\'an, 625600, China.
Comb Chem High Throughput Screen. 2022;25(10):1722-1730. doi: 10.2174/1386207324666210816123508.
Septic shock is sepsis accompanied by hemodynamic instability and high clinical mortality.
GSE95233, GSE57065, GSE131761 gene-expression profiles of healthy control subjects and septic shock patients were downloaded from the Gene-Expression Omnibus (GEO) database, and differences of expression profiles and their intersection were analysed using GEO2R. Function and pathway enrichment analysis was performed on common differentially expressed genes (DEG), and key genes for septic shock were screened using a protein-protein interaction network created with STRING. Also, data from the GEO database were used for survival analysis for key genes, and a meta-analysis was used to explore expression trends of core genes. Finally, high-throughput sequencing using the blood of a murine sepsis model was performed to analyse the expression of CD247 and FYN in mice.
A total of 539 DEGs were obtained (p < 0.05). Gene ontology analysis showed that key genes were enriched in functions, such as immune response and T cell activity, and DEGs were enriched in signal pathways, such as T cell receptors. FYN and CD247 are in the centre of the protein-protein interaction network, and survival analysis found that they are positively correlated with survival from sepsis. Further, meta-analysis results showed that FYN could be useful for the prognosis of patients, and CD247 might distinguish between sepsis and systemic inflammatory response syndrome patients. Finally, RNA sequencing using a mouse septic shock model showed low expression of CD247 and FYN in this model.
FYN and CD247 are expected to become new biomarkers of septic shock.
感染性休克是伴有血流动力学不稳定和高临床死亡率的败血症。
从基因表达综合数据库(GEO)下载了健康对照和感染性休克患者的 GSE95233、GSE57065 和 GSE131761 基因表达谱,使用 GEO2R 分析了差异表达谱及其交集。对常见差异表达基因(DEG)进行功能和通路富集分析,使用 STRING 构建的蛋白质-蛋白质相互作用网络筛选感染性休克的关键基因。还使用 GEO 数据库中的数据进行关键基因的生存分析,并进行荟萃分析以探索核心基因的表达趋势。最后,使用小鼠感染性休克模型的血液进行高通量测序,分析小鼠 CD247 和 FYN 的表达。
共获得 539 个 DEG(p<0.05)。基因本体论分析表明,关键基因富集在免疫反应和 T 细胞活性等功能中,DEG 富集在 T 细胞受体等信号通路中。FYN 和 CD247 位于蛋白质-蛋白质相互作用网络的中心,生存分析发现它们与感染性休克的生存呈正相关。此外,荟萃分析结果表明 FYN 可用于预测患者的预后,而 CD247 可能有助于区分感染性休克和全身炎症反应综合征患者。最后,使用小鼠感染性休克模型的 RNA 测序显示该模型中 CD247 和 FYN 的表达较低。
FYN 和 CD247 有望成为感染性休克的新生物标志物。