Department of Emergency Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, China.
Biosci Rep. 2020 Oct 30;40(10). doi: 10.1042/BSR20202649.
Sepsis is a common clinical disease with high mortality, and patients with sepsis have varied prognoses. Researchers need to explore the underlying mechanisms that determine the prognosis of sepsis. Hence, a mouse model was used to evaluate new potential prognostic markers of sepsis. Mice were randomly divided into low-dose group (n=3, lipopolysaccharides [LPS], 20 mg/kg) and high-dose group (n=3; LPS, 40 mg/kg). Total RNA was extracted from the peripheral blood of mice, and samples were then subjected to RNA sequencing. When complete data were normalized, the high-dose group and low-dose group were screened for differentially expressed genes (DEGs, log2FC ≥ 1 and q value ≤ 0.05). DEGs were analyzed by gene ontology enrichment, and potential core genes were screened using protein-protein interaction (PPI) network and weighted gene co-expression network analysis (WGCNA). Moreover, the survival data in GSE65682 were used to observe the correlation between core genes and prognosis. A total of 967 DEGs were identified in the low-dose group, of which 390 were up-regulated and 577 were down-regulated. These genes were mainly enriched in white blood cell activation, lymphocyte activation, immune system response etc. LCK, ZAP70, ITK, CD247, and DOCK2 were found at the core of PPI network, while WGCNA found that interferon-inducible protein 35 (IFI35), ITGB3, and mediator complex subunit 25 (MED25) may be potential core genes. It was demonstrated that CD247, DOCK2, IFI35, ITK, and LCK core genes were positively correlated with prognosis based on GSE65682. CD247, DOCK2, IFI35, ITK, LCK, and MED25 might be important targets affecting the prognosis of sepsis.
脓毒症是一种常见的临床疾病,死亡率高,且脓毒症患者的预后差异较大。研究人员需要探索决定脓毒症预后的潜在机制。因此,建立了一个小鼠模型来评估脓毒症新的潜在预后标志物。将小鼠随机分为低剂量组(n=3,脂多糖[LPS],20mg/kg)和高剂量组(n=3;LPS,40mg/kg)。从小鼠外周血中提取总 RNA,然后进行 RNA 测序。当数据完全标准化后,筛选高剂量组和低剂量组的差异表达基因(DEGs,log2FC≥1,q 值≤0.05)。对 DEGs 进行基因本体论富集分析,并通过蛋白质-蛋白质相互作用(PPI)网络和加权基因共表达网络分析(WGCNA)筛选潜在的核心基因。此外,还使用 GSE65682 中的生存数据观察核心基因与预后的相关性。在低剂量组中鉴定出 967 个差异表达基因,其中 390 个上调,577 个下调。这些基因主要富集在白细胞激活、淋巴细胞激活、免疫系统反应等方面。在 PPI 网络中发现 LCK、ZAP70、ITK、CD247 和 DOCK2 处于核心地位,而 WGCNA 发现干扰素诱导蛋白 35(IFI35)、ITGB3 和介导复合物亚基 25(MED25)可能是潜在的核心基因。基于 GSE65682 表明,CD247、DOCK2、IFI35、ITK、LCK 和 MED25 核心基因与预后呈正相关。CD247、DOCK2、IFI35、ITK、LCK 和 MED25 可能是影响脓毒症预后的重要靶点。