Upregulation of G Protein-Coupled Receptor 84 Contributes to the Early Prediction of Sepsis

Abstract

Background: Sepsis has been the main cause of mortality in patients in the world. The present study aimed to identify and validate the key genes involved in the development of sepsis. Methods: Gene expression profiles obtained from GSE35590 were used to screen the differentially expressed genes (DEGs) after endotoxin stimulation. Then, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were carried out to analyze the function of hub genes. The G protein-coupled receptor 84 (GPR84) with the greatest fold change was used as the target gene. The upregulation of GPR84 was validated in THP1, RAW264.7 cells and cecal ligation and puncture (CLP) animal model. Moreover, the predictive ability of GPR84 was evaluated by the area under curve (AUC) in two sepsis datasets. Results: In total, 267 genes were differentially expressed at three time points. Especially, GPR84 had 39.8, 28.7 and 15.8 folds changes at three time points. The GO and KEGG analysis indicated that GPR84 was mainly correlated with the neutrophil degranulation, immune response-regulating signaling pathway, and immune response-activating signal transduction. Then, the upregulation of GPR84 was validated in the whole blood, THP-1 cells and RAW264.7 cells under lipopolysaccharides (LPS) stimulation. Meanwhile, we also validated the overexpression of GPR84 in sepsis animals and patients. The results indicated that GPR84 may be utilized to predict the risk of sepsis with the AUC of 0.765 (0.649–0.858) in GSE9960 and 0.759 (0.666–0.837) in GSE74224. Conclusions: This study concluded that upregulated GPR84 may be a target gene for the development of sepsis, and GPR84 could be used to predict the incidence of sepsis. Clinical Trial Registration: Chinese clinical trial registry: ChiCTR2200064742.