SKAP1, FYN and CD3E Are Potential Biomarkers and Therapeutic Targets of Sepsis.

Abstract

Background: Sepsis is a systemic inflammatory response caused by pathogen infection, leading tomultiple organ failure. This study aims to identify potential sepsis biomarkers.

Methods: Differentially expressed genes in sepsis-related datasets GSE57065 and GSE95233 were analyzed, and sepsis-associated genes were identified using weighted gene co-expression network analysis. Protein-protein interaction network was further analyzed to screen the core genes, which were verified using external datasets GSE65682 and GSE9960. An in vitro septic cardiomyopathy model was constructed by inducing H9c2 cells with lipopolysaccharide (LPS).

Results: TCF7, LEF1, FYN, IL7R, CD3E, SKAP1 and FCER1G showed significant differences between sepsis and the control samples, and were related with immune cells infiltration. Sepsis patients with high expression of SKAP1, FYN and CD3E had better prognosis. Overexpression of SKAP1, FYN and CD3E could significantly inhibit the levels of inflammatory counterfactors TNF-α, IL-6 and IL-8 induced by LPS, and reduce the apoptosis rate of H9c2 cardiomyocytes, the ratio of cleaved caspase 3 and Bax/Bcl-2. Additionally, SKAP1 and FYN exerted these biological functions partially via activating PI3K/Akt pathway.

Conclusion: SKAP1, FYN and CD3E are potential sepsis biomarkers associsted with favorable prognosis, protecting against inflammation and cardiomyocyte apoptosis.