A genomic score prognostic of outcome in trauma patients

H. Shaw Warren, Constance M. Elson, Douglas L. Hayden, David A. Schoenfeld, J. Perren Cobb, Ronald V. Maier, Lyle L. Moldawer, Ernest E. Moore, Brian G. Harbrecht, Kimberly Pelak, Joseph Cuschieri, David Herndon, Marc G. Jeschke, Celeste Finnerty, Bernard H. Brownstein, Laura Hennessy, Philip H. Mason, Ronald G. Tompkins

Research output: Contribution to journalArticle

53 Citations (Scopus)

Abstract

Traumatic injuries frequently lead to infection, organ failure, and death. Health care providers rely on several injury scoring systems to quantify the extent of injury and to help predict clinical outcome.Physiological,anatomical, and clinical laboratory analytic scoring systems (Acute Physiology and Chronic Health Evaluation [APACHE], Injury Severity Score [ISS]) are utilized, with limited success, to predict outcome following injury.The recent development of techniques for measuring the expression level of all of a person's genes simultaneously may make it possible to develop an injury scoring system based on the degree of gene activation.We hypothesized that a peripheral blood leukocyte gene expression score could predict outcome, including multiple organ failure, following severe blunt trauma. To test such a scoring system,we measured gene expression of peripheral blood leukocytes from patients within 12 h of traumatic injury. cRNA derived from whole blood leukocytes obtained within 12 h of injury provided gene expression data for the entire genome that were used to create a composite gene expression score for each patient. Total blood leukocytes were chosen because they are active during inflammation,which is reflective of poor outcome.The gene expression score combines the activation levels of all the genes into a single number which compares the patient's gene expression to the average gene expression in uninjured volunteers. Expression profiles from healthy volunteers were averaged to create a reference gene expression profile which was used to compute a difference from reference (DFR) score for each patient. This score described the overall genomic response of patients within the first 12 h following severe blunt trauma. Regression models were used to compare the association of the DFR, APACHE, and ISS scores with outcome.We hypothesized that patients with a total gene response more different from uninjured volunteers would tend to have poorer outcome than those more similar.Our data show that for measures of poor outcome,such as infections,organ failures, and length of hospital stay, this is correct. DFR scores were associated significantly with adverse outcome, including multiple organ failure, duration of ventilation, length of hospital stay,and infection rate.The association remained significant after adjustment for injury severity as measured by APACHE or ISS. A single score representing changes in gene expression in peripheral blood leukocytes within hours of severe blunt injury is associated with adverse clinical outcomes that develop later in the hospital course. Assessment of genome-wide gene expression provides useful clinical information that is different from that provided by currently utilized anatomic or physiologic scores.

Original languageEnglish (US)
Pages (from-to)220-227
Number of pages8
JournalMolecular Medicine
Volume15
Issue number7-8
DOIs
StatePublished - Jul 2009

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Gene Expression
Wounds and Injuries
Leukocytes
Injury Severity Score
APACHE
Length of Stay
Multiple Organ Failure
Volunteers
Genome
Genes
Complementary RNA
Nonpenetrating Wounds
Cross Infection
Infection
Transcriptome
Health Personnel
Transcriptional Activation
Ventilation
Healthy Volunteers
Outcome Assessment (Health Care)

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine
  • Genetics(clinical)

Cite this

Warren, H. S., Elson, C. M., Hayden, D. L., Schoenfeld, D. A., Cobb, J. P., Maier, R. V., ... Tompkins, R. G. (2009). A genomic score prognostic of outcome in trauma patients. Molecular Medicine, 15(7-8), 220-227. https://doi.org/10.2119/molmed.2009.00027

A genomic score prognostic of outcome in trauma patients. / Warren, H. Shaw; Elson, Constance M.; Hayden, Douglas L.; Schoenfeld, David A.; Cobb, J. Perren; Maier, Ronald V.; Moldawer, Lyle L.; Moore, Ernest E.; Harbrecht, Brian G.; Pelak, Kimberly; Cuschieri, Joseph; Herndon, David; Jeschke, Marc G.; Finnerty, Celeste; Brownstein, Bernard H.; Hennessy, Laura; Mason, Philip H.; Tompkins, Ronald G.

In: Molecular Medicine, Vol. 15, No. 7-8, 07.2009, p. 220-227.

Research output: Contribution to journalArticle

Warren, HS, Elson, CM, Hayden, DL, Schoenfeld, DA, Cobb, JP, Maier, RV, Moldawer, LL, Moore, EE, Harbrecht, BG, Pelak, K, Cuschieri, J, Herndon, D, Jeschke, MG, Finnerty, C, Brownstein, BH, Hennessy, L, Mason, PH & Tompkins, RG 2009, 'A genomic score prognostic of outcome in trauma patients', Molecular Medicine, vol. 15, no. 7-8, pp. 220-227. https://doi.org/10.2119/molmed.2009.00027
Warren HS, Elson CM, Hayden DL, Schoenfeld DA, Cobb JP, Maier RV et al. A genomic score prognostic of outcome in trauma patients. Molecular Medicine. 2009 Jul;15(7-8):220-227. https://doi.org/10.2119/molmed.2009.00027
Warren, H. Shaw ; Elson, Constance M. ; Hayden, Douglas L. ; Schoenfeld, David A. ; Cobb, J. Perren ; Maier, Ronald V. ; Moldawer, Lyle L. ; Moore, Ernest E. ; Harbrecht, Brian G. ; Pelak, Kimberly ; Cuschieri, Joseph ; Herndon, David ; Jeschke, Marc G. ; Finnerty, Celeste ; Brownstein, Bernard H. ; Hennessy, Laura ; Mason, Philip H. ; Tompkins, Ronald G. / A genomic score prognostic of outcome in trauma patients. In: Molecular Medicine. 2009 ; Vol. 15, No. 7-8. pp. 220-227.
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