Department of Emergency Medicine, Affiliated Hospital of Southwest Medical University, Luzhou, 646000, Sichuan, China.
Department of Pediatrics, Ya'an Second People's Hospital, Ya'an, China.
Sci Rep. 2023 Mar 14;13(1):4258. doi: 10.1038/s41598-022-23062-7.
To screen potential pivotal targets in sepsis through peripheral blood. Septic patients (n = 23) and healthy volunteers (n = 10) were enrolled according to SEPSIS 3.0. Peripheral blood was collected within 24 h of enrollment, RNA-seq was performed on the peripheral blood. The sequencing data was screened for DEGs (p < 0.01; logFC ≥ 2). PPI, WGCNA and survival curve analysis were used to identify potential targets. Then, 5 PBMC samples were conducted by single-cell sequencing for cell lineage location. Finally, mouse sepsis model and clinic samples were performed to verify the targets gene using RNA-seq and RT-PCR, respectively. Compared to the control group, 1007 DEGs were found in septic group. BCL9L, BCL11B, CD247, CD96, MAFG and SAMD3 were in the core of network. These six genes correlated to the survival rate of septic patients and they were mainly expressed in T cells, except that MAFG was located in monocyte cell. The expression levels of six key genes were confirmed by animal and clinical samples. BCL9L, BCL11B, CD247, CD96 and SAMD3 were decreased in sepsis and mainly expressed in the T cell; while MAFG increased in sepsis and localizes to monocytes. These genes may be therapeutic targets for sepsis.
通过外周血筛选脓毒症潜在关键靶点。根据 SEPSIS 3.0 标准,纳入 23 例脓毒症患者和 10 例健康志愿者。在入组后 24 小时内采集外周血,对其进行 RNA-seq 检测。筛选外周血差异表达基因(DEGs)(p<0.01;logFC≥2)。利用 PPI、WGCNA 和生存曲线分析,识别潜在靶点。然后,对 5 例 PBMC 样本进行单细胞测序,以确定细胞谱系定位。最后,通过 RNA-seq 和 RT-PCR 分别在脓毒症小鼠模型和临床样本中验证目标基因。与对照组相比,脓毒症组发现 1007 个 DEGs。BCL9L、BCL11B、CD247、CD96、MAFG 和 SAMD3 位于网络的核心位置。这六个基因与脓毒症患者的生存率相关,它们主要在 T 细胞中表达,除了 MAFG 位于单核细胞中。通过动物和临床样本验证了这六个关键基因的表达水平。在脓毒症中,BCL9L、BCL11B、CD247、CD96 和 SAMD3 的表达水平降低,主要在 T 细胞中表达;而 MAFG 在脓毒症中增加,定位在单核细胞。这些基因可能是脓毒症的治疗靶点。