Identification of differentially expressed genes, transcription factors, microRNAs and pathways in neutrophils of sepsis patients through bioinformatics analysis

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.

The ‘analysis of gene expression and biomarkers for point-of-care decision support in Sepsis‘ study; temporal clinical parameter analysis and validation of early diagnostic biomarker signatures for severe inflammation andsepsis-SIRS discrimination

“…Providing external validation to our findings, several genes, such as CD177, ARG1 (arginase), MMP9, OLAH and ADM have been described previously as having important inflammatory roles in sepsis ( 16 , 29 , 41 , 42 , 44 , 51 – 71 ). ARG1 in particular has been identified by other groups as a good biomarker for sepsis diagnosis ( 64 ), specifically associated with neutrophil activity ( 72 ) a component of which may be from a myeloid-derived suppressor cell (MDSC) phenotype ( 60 ). These have been postulated to promote immune-suppression during sepsis and may also serve the same function in SIRS due to surgery or trauma ( 73 , 74 ), perhaps due to arginase suppression of T-cell function ( 55 , 56 , 63 , 75 ).…”

Predictive Value of High Mobility Group Box-1 and miR-146b in Septic Shock Patients

“…Recent studies have proved the association of miRNAs with the development of sepsis. It has been determined that gene-specific reprogramming through a miRNA-dependent mechanism can independently suppress the transcription and translation of proinflammatory genes [20,21] . MiR-146 may play a crucial role in developing sepsis by suppressing the production of inflammatory cytokines [22] .…”