Feng Anlin, Rice Amanda D, Zhang Yao, Kelly Gabriel T, Zhou Tong, Wang Ting
Department of Internal Medicine, College of Medicine-Phoenix, University of Arizona, Phoenix, Arizona.
Key Laboratory of Anhui Province for Infection and Immunology, Bengbu Medical College, Anhui, China.
Shock. 2020 Mar;53(3):284-292. doi: 10.1097/SHK.0000000000001376.
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 an S1PR1-related gene signature for prediction of survival in sepsis patients has yet to be identified. This study aims to find S1PR1-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.
Gene expression analysis from sepsis patients enrolled in published datasets from Gene Expression Omnibus was utilized to identify both S1PR1-related genes (co-expression genes or functional-related genes) and sepsis survival-related genes.
We identified 62-gene and 16-gene S1PR1-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.
Our results have confirmed the significant involvement of S1PR1-dependent genes in the development of sepsis and provided new gene signatures for predicting survival of sepsis patients.
脓毒症是一种潜在的危及生命的潜在感染并发症，可迅速引发多器官系统的组织损伤。迄今为止，尚无用于预测脓毒症患者生存的有效预后生物标志物。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，尚未确定用于预测脓毒症患者生存的与S1PR1相关的基因特征。本研究旨在通过外周血基因表达谱寻找可预测脓毒症患者生存的S1PR1相关生物标志物，用作潜在的预后和诊断工具。
利用基因表达综合数据库中已发表数据集中脓毒症患者的基因表达分析，来识别与S1PR1相关的基因（共表达基因或功能相关基因）以及脓毒症生存相关基因。
我们在发现队列中确定了与脓毒症患者生存相关的62基因和16基因的S1PR1相关分子特征（SMS）。这两个SMS基因在多个关键免疫相关途径中显著富集，这些途径在脓毒症发展中起关键作用。同时，该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，作为新开发的基因特征，我们的SMS在脓毒症生存预后方面的表现明显优于具有相同基因数量的随机基因特征。
我们的结果证实了S1PR1依赖性基因在脓毒症发展中的重要作用，并为预测脓毒症患者的生存提供了新的基因特征。
