Comprehensive Analysis of Common Different Gene Expression Signatures in the Neutrophils of Sepsis

Abstract

The central component of sepsis pathogenesis is inflammatory disorder, which is related to dysfunction of the immune system. However, the specific molecular mechanism of sepsis has not yet been fully elucidated. The aim of our study was to identify genes that are significantly changed during sepsis development, for the identification of potential pathogenic factors. Differentially expressed genes (DEGs) were identified in 88 control and 214 septic patient samples. Gene ontology (GO) and pathway enrichment analyses were performed using David. A protein-protein interaction (PPI) network was established using STRING and Cytoscape. Further validation was performed using real-time polymerase chain reaction (RT-PCR). We identified 37 common DEGs. GO and pathway enrichment indicated that enzymes and transcription factors accounted for a large proportion of DEGs; immune system and inflammation signaling demonstrated the most significant changes. Furthermore, eight hub genes were identified via PPI analysis. Interestingly, four of the top five upregulated and all downregulated DEGs were involved in immune and inflammation signaling. In addition, the most intensive hub gene AKT1 and the top DEGs in human clinical samples were validated using RT-PCR. This study explored the possible molecular mechanisms underpinning the inflammatory, immune, and PI3K/AKT pathways related to sepsis development.

Leukocyte Phenotyping in Sepsis Using Omics, Functional Analysis, and in Silico Modeling

“…Genomics and transcriptomics have been used to reveal mechanisms of innate immune cell function, specifically neutrophils, in sepsis (12,32). For example, a retrospective study used publicly available gene expression profiles (i.e., GEO database) of neutrophils from whole blood to identify key genes and pathways associated with neutrophils during sepsis via bioinformatics (32). Authors identified DEGs from neutrophils (day 3-4 and day 6-8 post septic shock) in patients with sepsis-induced immunosuppression.…”

“…Authors identified DEGs from neutrophils (day 3–4 and day 6–8 post septic shock) in patients with sepsis-induced immunosuppression. Upregulated DEGs such as Mmp8, IL-15, Nfkbia, and downregulated DEGs including HLA genes (e.g., Hla-dma) and IFN-related genes (e.g., Ifi6, Ifit1) were identified as potential targets for immunotherapy management and demonstrated that neutrophils are the primary target cells for immune-stimulating therapies (e.g., antiprogrammed cell death 1 [anti-PD1], IL-7, IL-15) (32). Both studies identified Akt1 as significantly dysregulated and thus warrant further functional investigation in neutrophils.…”