C3AR1 is a regulatory factor associated with coagulation cascade and inflammation in sepsis

Abstract

Sepsis is a leading cause of mortality in intensive care units. Sepsis is associated with activation of the coagulation cascade and inflammation. The aim of this study was to identify coagulation-related genes in sepsis that may provide translational potential therapeutic targets. The datasets GSE28750, GSE95233, and GSE65682 were downloaded from the gene expression omnibus database. Consensus-weighted gene co-expression network analysis (WGCNA) was used to identify sepsis modules. Gene set enrichment analysis was used to identify genes enriched in the coagulation cascade. The value of hub-gene in immunological analysis was tested in the validation sets (GSE95233). The value of hub-gene in clinical prognosis was tested in the validation sets (GSE65582). One thousand one hundred seventy-six genes with high connectivity in the clinically significant module were identified as hub genes. Ten genes were found to be enriched in coagulation-related signaling pathways. C3AR1 was selected for further analysis. The immune infiltration analysis showed that lower expression of C3AR1 was associated with immune response in sepsis and could be an independent predictor of survival status in sepsis patients. Meanwhile, univariate and multivariate Cox analysis showed that C3AR1 had a significant correlation with survival. C3AR1 may become an effective biomarker for worse outcomes in sepsis patients associated with immune and coagulation cascade.