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一个新型的与凋亡相关的基因标志物可预测脓毒症患者的预后,并揭示免疫浸润情况。

A novel anoikis-related gene signature predicts prognosis in patients with sepsis and reveals immune infiltration.

机构信息

Department of Emergency, The First Affiliated Hospital of Chengdu Medical College, Chengdu, 610500, Sichuan, People's Republic of China.

School of Public Health, Chengdu Medical College, Chengdu, 610500, Sichuan, People's Republic of China.

出版信息

Sci Rep. 2024 Jan 28;14(1):2313. doi: 10.1038/s41598-024-52742-9.

Abstract

Sepsis is a common acute and severe medical condition with a high mortality rate. Anoikis, an emerging form of cell death, plays a significant role in various diseases. However, the role of anoikis in sepsis remains poorly understood. Based on the datasets from Gene Expression Omnibus and anoikis-related genes from GeneCards, the differentially expressed anoikis-related genes (DEARGs) were identified. Based on hub genes of DEARGs, a novel prognostic risk model was constructed, and the pattern of immune infiltration was investigated by CIBERSORT algorithm. And small molecule compounds targeting anoikis in sepsis were analyzed using Autodock. Of 23 DEARGs, CXCL8, CFLAR, FASLG and TP53 were significantly associated with the prognosis of sepsis (P < 0.05). Based on the prognostic risk model constructed with these four genes, high-risk population of septic patients had significant lower survival probability than low-risk population (HR = 3.30, P < 0.001). And the level of CFLAR was significantly correlated with the number of neutrophils in septic patients (r = 0.54, P < 0.001). Moreover, tozasertib had low binding energy with CXCL8, CFLAR, FASLG and TP53, and would be a potential compound for sepsis. Conclusively, our results identified a new prognostic model and potential therapeutic molecular for sepsis, providing new insights on mechanism and treatment of sepsis.

摘要

脓毒症是一种常见的急性严重疾病,死亡率很高。凋亡,一种新兴的细胞死亡形式,在各种疾病中起着重要作用。然而,凋亡在脓毒症中的作用仍知之甚少。基于基因表达综合数据库和基因卡片中的凋亡相关基因,鉴定了差异表达的凋亡相关基因(DEARGs)。基于 DEARGs 的枢纽基因,构建了一个新的预后风险模型,并通过 CIBERSORT 算法研究了免疫浸润模式。并使用 Autodock 分析了针对脓毒症中凋亡的小分子化合物。在 23 个 DEARGs 中,CXCL8、CFLAR、FASLG 和 TP53 与脓毒症的预后显著相关(P<0.05)。基于这四个基因构建的预后风险模型,脓毒症高危人群的生存概率明显低于低危人群(HR=3.30,P<0.001)。而且,CFLAR 的水平与脓毒症患者中性粒细胞的数量显著相关(r=0.54,P<0.001)。此外,tozasertib 与 CXCL8、CFLAR、FASLG 和 TP53 的结合能较低,可能是脓毒症的潜在化合物。总之,我们的研究结果确定了一个新的脓毒症预后模型和潜在的治疗分子,为脓毒症的发病机制和治疗提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c50/10822872/bb3b9fe6817e/41598_2024_52742_Fig1_HTML.jpg

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