Identification of potential crucial genes and biomarkers from neutrophils in sepsis using bioinformatics analysis

Abstract

Sepsis is a complex series of immune responses to infection and is commonly associated with acquired immunodeficiency. The current study aimed to identify the biomarkers of sepsis. Differential expression analysis and protein-protein interaction analysis were conducted to explore potential biomarkers. Gene Ontology enrichment analysis and Kyoto Encyclopedia of Genes and Genomes analysis were performed to explore potential mechanisms. The Immune Cell Abundance Identifier website was utilized to evaluate immune cell infiltration in the whole blood. Receiver operating characteristic curve and area under the curve were applied to compare the prognostic accuracy of hub genes. Six genes were selected via differentially expressed gene analysis and protein-protein interaction analysis. Furthermore, CTSD, GADD45A, MAPK14, MMP9, and VIM were selected via validation analysis of independent datasets. Immune infiltration analysis showed that CTSD, GADD45A, MAPK14, MMP9, and VIM may regulate immune cells via neutrophils. Patients with sepsis had a significantly higher expression of CTSD, GADD45A, MAPK14, MMP9, and VIM than normal health controls. The area under the curve of CTSD, GADD45A, MAPK14, MMP9, and VIM were 0.90 (0.83-0.97), 0.89 (0.81-0.96), 0.91 (0.84-0.87), 0.95 (0.91-1.00), and 0.95 (0.91-1.00), respectively. According to the validation result of RT-PCR, only MAPK14 was significantly upregulated compared with controls, which was concordant with the bioinformatics analysis results. This study identified several potential diagnostic genes including CTSD, GADD45A, MAPK14, MMP9, and VIM. These genes may regulate the expression of immune cells via neutrophils in the development of sepsis.