Identification of risk factors for sepsis-associated mortality by gene expression profiling analysis

Abstract

Sepsis is a common cause of mortality due to systemic infection. Although numerous studies have investigated this life-threatening condition, there remains a lack of suitable markers to evaluate the severity of sepsis. The present study focused on the identification of risk factors for sepsis‑associated mortality by genome‑wide expression profiling. Initially, the GEO2R web tool was used to identify the differentially expressed genes (DEGs) between sepsis survivors and nonsurvivors. It was identified that the upregulated DEGs in the nonsurvivors compared with survivors were highly enriched in the type I interferon (IFN‑I) signaling pathway. Furthermore, the associations of the upregulated genes were analyzed by STRING and the results demonstrated that a set of proteins in IFN‑I signaling pathway closely interacted with each other. To further investigate whether the IFN‑I signaling pathway is dysregulated in a subset of patients with a high risk of mortality due to sepsis, in this case neonates, the DEGs between the cord blood mononuclear cells of neonates and adult peripheral blood mononuclear cells were analyzed. It was identified that DEGs were not enriched in IFN‑I signaling in the blood of untreated neonates and adults; however, IFN‑I signaling was upregulated in the lipopolysaccharide (LPS)‑treated cord blood mononuclear cells of healthy neonates compared with the LPS‑treated peripheral blood mononuclear cells of adults. In addition, these data revealed that the proteins involved in the IFN‑I signaling pathway possessed a higher number of interacting partners. These results indicated that upregulated IFN‑I signaling may be a high-risk factor for mortality due to sepsis.

Inhibiting DNA Methylation Improves Survival in Severe Sepsis by Regulating NF-κB Pathway

“…RNA sequencing analysis not only revealed a tight clustering between sepsis patients and healthy individuals but also between survived and non-survived patients with sepsis, consistent with previous studies (37,38).…”

Proteomic changes associated with racial background and sepsis survival outcomes

“…Gene expression profiling of neonatal sepsis patients has revealed that in early sepsis, several genes related to interferon 1 signaling are decreased in survivors and that increased interferon 1 signaling is associated with mortality. 90 Additionally, plasma levels of type I interferons were increased in African American patients with SLE compared to White patients with SLE in a luciferase assay. 91 Conversely, genotyping of SLE patients revealed a SNP in the MAVS gene, which can induce type I interferon expression, that was found almost exclusively in African American patients and that correlated to low type I interferon and pro-inflammatory molecule production.…”

Underlying Vulnerabilities to the Cytokine Storm and Adverse COVID-19 Outcomes in the Aging Immune System

“…Chronic disease states and obesity appear to track closely with this, but there are likely important genetic and environmental reasons that are operant across age groups. For example, there are several polymorphisms in inflammatory cytokine-related genes that make individuals more or less susceptible to inflammatory pathway cascade signaling ( 66 ) and hence to development of or protection from cytokine storm. Environmental risk factors, such as smoking (tobacco, electronic-cigarette, or marijuana), chronic infections, such as CMV or HIV, and nutritional deficiencies, such as Vitamin D are known to activate inflammatory pathways, potentially driving differential inflammatory pathway activation across all age groups ( 67 ).…”