title: Reactive oxygen species-associated molecular signature predicts survival in patients with sepsis.
abstract: Sepsis-related multiple organ dysfunction syndrome is a leading cause of death in intensive care units. There is overwhelming evidence that oxidative stress plays a significant role in the pathogenesis of sepsis-associated multiple organ failure; however, reactive oxygen species (ROS)-associated biomarkers and/or diagnostics that define mortality or predict survival in sepsis are lacking. Lung or peripheral blood gene expression analysis has gained increasing recognition as a potential prognostic and/or diagnostic tool. The objective of this study was to identify ROS-associated biomarkers predictive of survival in patients with sepsis. In-silico analyses of expression profiles allowed the identification of a 21-gene ROS-associated molecular signature that predicts survival in sepsis patients. Importantly, this signature performed well in a validation cohort consisting of sepsis patients aggregated from distinct patient populations recruited from different sites. Our signature outperforms randomly generated signatures of the same signature gene size. Our findings further validate the critical role of ROSs in the pathogenesis of sepsis and provide a novel gene signature that predicts survival in sepsis patients. These results also highlight the utility of peripheral blood molecular signatures as biomarkers for predicting mortality risk in patients with sepsis, which could facilitate the development of personalized therapies.
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Bime
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA.
authors.forename: Tong
authors.initials: T
authors.lastname: Zhou
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA.
authors.forename: Ting
authors.initials: T
authors.lastname: Wang
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA; Department of Biomedical Engineering, University of Arizona, Tucson, Arizona, USA.
authors.forename: Marvin J
authors.initials: MJ
authors.lastname: Slepian
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA.
authors.forename: Joe G N
authors.initials: JG
authors.lastname: Garcia
authors.affiliation: Department of Medicine, University of Arizona, Tucson, Arizona, USA; Southern Arizona Veterans Administration Health Care System, Tucson, Arizona, USA.
authors.forename: Louise
authors.initials: L
authors.lastname: Hecker
keywords: gene expression; microarray; reactive oxygen species; sepsis