NAMPT-associated gene signature in the prediction of severe sepsis.

ABSTRACT

OBJECTIVE: Sepsis is a life-threatening condition of severe organ dysfunction induced by uncontrolled infection and dysregulated host response. However, standardized clinical biomarkers for sepsis are needed to improve patient care, especially in intensive care units (ICUs). Nicotinamide phosphoribosyltransferase (NAMPT) regulates the activity of nicotinamide adenine dinucleotide (NAD)-dependent enzymes and modulates multiple metabolic pathways. Elevated NAMPT gene expression is a risk factor in the pathogenesis and development of sepsis, which is strongly linked to patient morbidity and ICU mortality. At present, there is no identified NAMPT gene signature for prognosis of sepsis patients. METHODS: By analyzing gene expression profiles in peripheral blood mononuclear cells, this study was designed to establish a NAMPT-associated biomarker that effectively predicts survival in sepsis patients. RESULTS: We obtained 19 common genes by intersecting NAMPT-associated genes and sepsis survival-related genes, and this 19-gene signature is significantly enriched in metabolic pathways and NF-κB pathways related to sepsis development. Notably, this 19-gene NAMPT signature was able to discriminate high-risk sepsis from low-risk sepsis in both discovery and validation cohorts. Furthermore, we confirmed that this 19-gene NAMPT signature performed significantly better for sepsis prognosis than random gene sets with 19 genes. CONCLUSIONS: We identified a novel NAMPT gene signature with effective prognostic power for sepsis. Further studies focusing on these biomarkers may also provide an early intervention system for sepsis treatment.