SOX18-associated gene signature predicts sepsis outcome

Objectives: Sepsis is a critical medical condition associated with an high mortality. Currently, there are no reliable diagnostic or prognostic biomarkers to evaluate sepsis outcomes. SRY (sex-determining region on the Y chromosome)-box transcription factor 18 (SOX18) is an endothelial barrier protective protein, and a decreased level of SOX18 expression is involved in disruption of human endothelial cell barrier integrity. Over-expression of SOX18 attenuates the bacterial lipopolysaccharide (LPS)-mediated disruption of the vascular barrier and is associated with favorable prognosis. The utility of SOX18-related genes as biomarkers in sepsis is uncertain. Methods: Transcriptomic analysis was used to profile the PBMC samples of patients with sepsis across two Gene Expression Omnibus (GEO) datasets with survival data. An 84-gene signature was derived from discovery datasets that correlated with SOX18 gene expression and sepsis survival. Results: Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed Th1 and Th2 cell differentiation, Cytokine-cytokine receptor interaction, and T cell receptor signaling pathways as the most significantly enriched KEGG pathways among 84 genes. A severity score based on the gene expression of 84 genes was allocated to each patient. A notable increase was detected in sepsis patients compared to healthy controls in both discovery and validation cohorts. SOX18-associated gene signature discriminated severe cases from mild cases and performed significantly better than both random 84-gene sets from whole genomes or sepsis survival-related genes. Furthermore, we obtained an 18-gene signature from screening these 84 genes in a LASSO model, which performed better in both discovery and validation cohorts. Conclusions: Data support SOX18-associated gene signatures as a prognostic biomarker for sepsis.