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Abstract
BackgroundSepsis 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.MethodsThis 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.ResultsWe 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.ConclusionsOur 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.
Highlights
Sepsis is a life-threatening complication of infection that rapidly triggers tissue damage in multiple organ systems and leads to multi-organ deterioration
We examined whole blood gene expression in two standalone cohorts from Gene Expression Omnibus (GEO) and identified a gene signature of 18 genes significantly associated both with S1P receptor 3 (S1PR3) and sepsis survival
Identification of an S1PR3‐related molecular signature (S3MS) associated with sepsis survival Firstly, we identified all S1PR3-interactive proteins
Summary
Sepsis is a life-threatening complication of infection that rapidly triggers tissue damage in multiple organ systems and leads to multi-organ deterioration. 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. The mortality of sepsis has risen unacceptably high with a 31% increase between 1999 and 2014 [2]. This elevation in mortality rate is partially due to the complexity of its immunological syndrome and multiorgan involvement [3]. An effective prognostic biomarker that can predict the clinical outcome of sepsis patients appropriately is in high demand in clinical practice. Single biomarkers lack specificity and sensitivity as prognostic tools for sepsis patients. Several studies [6, 7] attempted to combine proinflammatory and anti-inflammatory markers and is the method to most likely succeed in predicting the disease
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