Department of Internal Medicine, College of Medicine-Phoenix, University of Arizona, 475 N. 5th Street, Phoenix, AZ, 85004, USA.
Department of Medicine, College of Medicine-Tucson, University of Arizona, Tucson, AZ, USA.
BMC Med Genomics. 2021 Feb 6;14(1):43. doi: 10.1186/s12920-021-00886-2.
Sepsis is a life-threatening complication of infection that rapidly triggers tissue damage in multiple organ systems and leads to multi-organ deterioration. Up to date, prognostic biomarkers still have limitations in predicting the survival of patients with sepsis. We need to discover more prognostic biomarkers to improve the sensitivity and specificity of the prognosis of sepsis patients. Sphingosine-1-phosphate (S1P) receptor 3 (S1PR3), as one of the S1P receptors, is a prospective prognostic biomarker regulating sepsis-relevant events, including compromised vascular integrity, antigen presentation, and cytokine secretion. Until now, no S1PR3-related prognostic gene signatures for sepsis patients have been found.
This study intends to obtain an S1PR3-associated gene signature from whole blood samples to be utilized as a probable prognostic tool for patients with sepsis.
We obtained an 18-gene S1PR3-related molecular signature (S3MS) from the intersection of S1PR3-associated genes and survival-associated genes. Numerous important immunity pathways that regulate the progression of sepsis are enriched among our 18 genes. Significantly, S3MS functions greatly in both the discovery and validation cohort. Furthermore, we demonstrated that S3MS obtains significantly better classification performance than random 18-gene signatures.
Our results confirm the key role of S1PR3-associated genes in the development of sepsis, which will be a potential prognostic biomarker for patients with sepsis. Our results also focus on the classification performance of our S3MS as biomarkers for sepsis, which could also provide an early warning system for patients with sepsis.
脓毒症是一种危及生命的感染并发症，它会迅速引发多个器官系统的组织损伤，并导致多器官恶化。迄今为止，预测脓毒症患者生存的预后生物标志物仍存在局限性。我们需要发现更多的预后生物标志物，以提高脓毒症患者预后的灵敏度和特异性。鞘氨醇-1-磷酸（S1P）受体 3（S1PR3）作为 S1P 受体之一，是调节脓毒症相关事件的有前途的预后生物标志物，包括血管完整性受损、抗原呈递和细胞因子分泌。到目前为止，还没有发现与脓毒症患者相关的 S1PR3 预后基因特征。
本研究旨在从全血样本中获得与 S1PR3 相关的基因特征，作为脓毒症患者的一种可能的预后工具。
我们从 S1PR3 相关基因和生存相关基因的交集获得了一个 18 个基因的 S1PR3 相关分子特征（S3MS）。我们的 18 个基因中富集了许多调节脓毒症进展的重要免疫途径。重要的是，S3MS 在发现和验证队列中都有很好的作用。此外，我们还证明 S3MS 的分类性能明显优于随机的 18 个基因特征。
我们的研究结果证实了 S1PR3 相关基因在脓毒症发展中的关键作用，这将是脓毒症患者的一个潜在预后生物标志物。我们的研究结果还关注了我们的 S3MS 作为脓毒症生物标志物的分类性能，这也可为脓毒症患者提供一个早期预警系统。
