Abstract
Sepsis has been recognized to be a life-threatening organ dysfunction caused by the dysregulation of the host response to infections. Our work aims to screen key biomarkers related to neutrophils in sepsis using bioinformatics analysis. For this purpose, the microarray datasets related to neutrophils in sepsis patients were downloaded from the Gene Expression Omnibus (GEO) database. According to the Bayesian test, the Limma package in R was used to screen differentially expressed genes (DEGs). Then, DEGs were uploaded to the DAVID online diagnostic tool for subsequent Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment on the selected DEGs. Next, protein-protein interaction (PPI) network was established based on the selected DEGs using the STRING website and the Cytoscape software. Furthermore, according to the function of the iRegulon plug-in in Cytoscape, our study further predicts and established regulatory networks related to transcription factors and regulatory genes. In addition, the miRWalk2.0 database was used to search for miRNA-DEG pairs, associated with the conduction of intersections of miRNAs predicted by TargetScan, Miranda, miRDB and RNA22 databases. Then, these miRNA-DEG pairs were also displayed in the form of a regulatory network through Cytoscape. Finally, two datasets were selected to verify the screened genes, regulatory factors, and miRNAs, to plot receiver operating characteristics (ROC) curves and compute the area under the curve (AUC) values. The results showed that AKT1, MMP9, ARG1, ETS1 targeting AKT1, and has-miR-124-3p targeting RPS6KA5 may have diagnostic value for patients with sepsis and septic shock. While further experimental studies are required to confirm their role in septic neutrophils.
Highlights
Introduction sepsis treatmentFor example, inducing neutrophilSepsis causes life-threatening organ dysfunction autophagy may enhance the production of neutrophil caused by an imbalanced response of the host to extracellular traps (NETs), thereby protecting mice from infections
After the integration of 3 microarray data related to neutrophils of sepsis patients and normal subjects, the obtained differentially expressed genes (DEGs) were crossed with the screening of 603 DEGs in GSE64457, 695 in GSE123729, and 3,158 in GSE100150. [Figures S1(1), S1(2)-(6), S2(1), S2(2)-(6), S3(1) and S3(2)-(6)]
Gene Ontology (GO) enrichment analysis in our study showed that AKT serine/threonine kinase 1 (AKT1) and MMP9 were enriched in tumor necrosis factor (TNF) signaling pathway
Summary
Sepsis causes life-threatening organ dysfunction autophagy may enhance the production of neutrophil caused by an imbalanced response of the host to extracellular traps (NETs), thereby protecting mice from infections It has a high incidence, and the condition the lethality induced by sepsis [6]. It has been recognized to critical illness and sepsis, high levels of miR-133a are be a major health burden worldwide with considerable related to the severity of the disease and predict adverse economic consequences [3]. It is of great practical outcomes in critically ill patients [7]. Despite the above significance for exploring the molecular mechanism of studies, there is still a lack of comprehensive sepsis to benefit the development of novel therapeutic understanding of the genes and miRNAs that are approaches for this disease
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