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A Genomic Score Prognostic of Outcome in Trauma Patients

ABSTRACT: Physiological, anatomical, and clinical laboratory analytic scoring systems (APACHE, Injury Severity Score (ISS)) have been utilized, with limited success, to predict outcome following injury. We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. Contributor: The Inflammation and the Host Response to Injury Large Scale Collaborative Research Program Keywords: expression profiles

ORGANISM(S): Homo sapiens

PROVIDER: GSE11375 | GEO | 2009/04/13

SECONDARY ACCESSION(S): PRJNA106483

REPOSITORIES: GEO

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Project description:The study was aimed to identify mechanisms linked to complicated courses after severe trauma by a systems biology approach. In severe trauma, overwhelming systemic inflammation can result in adverse events and the development of complications, including sepsis. In a prospective study, RNA samples from circulating leukocytes from patients with multiple injury (injury severity score â¥ 17) were analyzed for dynamic changes in gene expression over a period of 21 days by whole genome screening. Based on their clinical presentation, patients were divided into two subgroups: patients with secondary sepsis after trauma (n=5) and patients with systemic inflammation without infection (n=5). Expression cluster were defined by correlating gene expression data with clinical outcome parameters. Using unsupervised clustering, patients with systemic inflammation only and patients with sepsis showed a distinct expression pattern and the discrimination of clinical presentation was reflected by clustering of the samples. Explorative gene set analysis revealed robust upregulation of genes related to âhemoglobin metabolism/oxygen transportâ and âpathogenic E.coli infectionâ. 10 patients with multi-system trauma (ISS â¥ 17 points) admitted to the Division of Trauma Surgery at the University Hospital Zurich were included. Whole blood from trauma patients was collected within the first 6 h after trauma (day 0) and on days 1, 2, 3, 5, 7, 10, 14, and 21. Total cellular RNA from circulating leukocytes was isolated using PaxGene Blood RNA Kit (PreAnalytix) for transcriptome profiling. RNA from blood of trauma patients was extracted and subjected to microarray analysis for comparison of longitudinal transcriptomic responses of patients. RNA samples of circulating leukocytes covering time points directly after admission (D0) and on the consecutive days (D1-D21) were subject to multifactorial microarray data analysis: Differences in dynamics of transcripts were assessed by contrasting time- and individual-resolved changes for sepsis and systemic inflammation without infection.

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A Genomic Score Prognostic of Outcome in Trauma Patients

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