S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis
S1PR1-Associated Molecular Signature Predicts Survival in Patients with Sepsis
复制标题
DOI：
10.1097/shk.0000000000001376
复制
发表时间：
2020-03-01
期刊：
影响因子：
3.1
通讯作者：
Wang, Ting
中科院分区：
文献类型：
--
作者：
Feng, Anlin;Rice, Amanda D.;Wang, Ting
背景资料：脓毒症是潜在感染的潜在危及生命的并发症，可迅速引发多器官系统的组织损伤。到目前为止，没有建立有用的预后生物标志物脓毒症生存预测。鞘氨醇-1-磷酸（S1P）及其受体S1P受体1（S1PR1）是脓毒症的潜在治疗靶点和生物标志物，因为两者都是脓毒症相关信号事件的活性调节剂。然而，一个S1PR1相关的基因标签的识别预测脓毒症患者的生存尚未确定。本研究旨在通过外周血S1PR1的基因表达谱，寻找能够预测脓毒症患者生存的S1PR1相关生物标志物，作为潜在的预后和诊断工具。研究方法：利用来自Gene Expression Omnibus的已发表数据集中登记的脓毒症患者的基因表达分析来鉴定S1PR1相关基因（共表达基因或功能相关基因）和脓毒症生存相关基因。结果如下：我们在发现队列中鉴定了与脓毒症患者生存相关的62个基因和16个基因S1PR1相关分子标记（SMS）。这两种SMS基因在已知在脓毒症发展中起关键作用的多个关键免疫相关途径中显著富集。同时，SMS在包含脓毒症患者的验证队列中表现良好。我们进一步证实了我们的SMS，作为新开发的基因签名，在脓毒症生存预后方面比具有相同基因大小的随机基因签名表现得更好。结论：我们的研究结果证实了S1 PR 1依赖性基因在脓毒症的发生中发挥着重要作用，并为预测脓毒症患者的生存提供了新的基因特征。
Background: Sepsis is a potentially life-threatening complication of an underlying infection that quickly triggers tissue damage in multiple organ systems. To date, there are no established useful prognostic biomarkers for sepsis survival prediction. Sphingosine-1-phosphate (S1P) and its receptor S1P receptor 1 (S1PR1) are potential therapeutic targets and biomarkers for sepsis, as both are active regulators of sepsis-relevant signaling events. However, the identification of anS1PR1-related gene signature for prediction of survival in sepsis patients has yet to be identified. This study aims to findS1PR1-associated biomarkers which could predict the survival of patients with sepsis using gene expression profiles of peripheral blood to be used as potential prognostic and diagnostic tools. Methods: Gene expression analysis from sepsis patients enrolled in published datasets from Gene Expression Omnibus was utilized to identify bothS1PR1-related genes (co-expression genes or functional-related genes) and sepsis survival-related genes. Results: We identified 62-gene and 16-geneS1PR1-related molecular signatures (SMS) associated with survival of patients with sepsis in discovery cohort. Both SMS genes are significantly enriched in multiple key immunity-related pathways that are known to play critical roles in sepsis development. Meanwhile, the SMS performs well in a validation cohort containing sepsis patients. We further confirmed our SMSs, as newly developed gene signatures, perform significantly better than random gene signatures with the same gene size, in sepsis survival prognosis. Conclusions: Our results have confirmed the significant involvement ofS1PR1-dependent genes in the development of sepsis and provided new gene signatures for predicting survival of sepsis patients.