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Determination of Burn Patient Outcome by Large-Scale Quantitative Discovery Proteomics

Finnerty, Celeste C. PhD1,2; Jeschke, Marc G. MD, PhD3; Qian, Wei-Jun PhD4; Kaushal, Amit MD, PhD5; Xiao, Wenzhong PhD5; Liu, Tao PhD4; Gritsenko, Marina A. MS4; Moore, Ronald J. BS4; Camp, David G. II PhD4; Moldawer, Lyle L. PhD6; Elson, Constance PhD7; Schoenfeld, David PhD7; Gamelli, Richard MD8; Gibran, Nicole MD9; Klein, Matthew MD9; Arnoldo, Brett MD10; Remick, Daniel MD11; Smith, Richard D. PhD4; Davis, Ronald PhD5; Tompkins, Ronald G. MD, ScD7; Herndon, David N. MD1

doi: 10.1097/CCM.0b013e31827c072e
Clinical Investigations

Objectives: Emerging proteomics techniques can be used to establish proteomic outcome signatures and to identify candidate biomarkers for survival following traumatic injury. We applied high-resolution liquid chromatography-mass spectrometry and multiplex cytokine analysis to profile the plasma proteome of survivors and nonsurvivors of massive burn injury to determine the proteomic survival signature following a major burn injury.

Design: Proteomic discovery study.

Setting: Five burn hospitals across the United States.

Patients: Thirty-two burn patients (16 nonsurvivors and 16 survivors), 19–89 years old, were admitted within 96 hours of injury to the participating hospitals with burns covering more than 20% of the total body surface area and required at least one surgical intervention.

Interventions: None.

Measurements and Main Results: We found differences in circulating levels of 43 proteins involved in the acute-phase response, hepatic signaling, the complement cascade, inflammation, and insulin resistance. Thirty-two of the proteins identified were not previously known to play a role in the response to burn. Interleukin-4, interleukin-8, granulocyte macrophage colony-stimulating factor, monocyte chemotactic protein-1, and β2-microglobulin correlated well with survival and may serve as clinical biomarkers.

Conclusions: These results demonstrate the utility of these techniques for establishing proteomic survival signatures and for use as a discovery tool to identify candidate biomarkers for survival. This is the first clinical application of a high-throughput, large-scale liquid chromatography-mass spectrometry-based quantitative plasma proteomic approach for biomarker discovery for the prediction of patient outcome following burn, trauma, or critical illness.

1 Department of Surgery, University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX.

2 Institute for Translational Sciences, Sealy Center for Molecular Medicine, University of Texas Medical Branch, Galveston, TX.

3 Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre and Division of Plastic Surgery, University of Toronto, Toronto, ON, Canada.

4 Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA.

5 Stanford Genome Technology Center, Stanford University School of Medicine, Stanford, CA.

6 Department of Surgery, University of Florida College of Medicine, Gainesville, FL.

7 Department of Surgery, Massachusetts General Hospital, Shriners Hospital For Children, and Harvard Medical School, Boston, MA.

8 Department of Surgery, Loyola University Stritch School of Medicine, Maywood, IL.

9 Department of Surgery, University of Washington School of Medicine, Harborview Medical Center, Seattle, WA.

10 Department of Surgery, University of Texas Southwestern Medical School, Dallas, TX.

11 Boston University School of Medicine, Boston, MA.

Drs. Finnerty, Jeschke, Qian, and Kaushal contributed equally to the work presented in this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal).

Supported, in part, by a Large Scale Collaborative Research Grant from the National Institute of General Medical Sciences (U54 GM-62119-04) awarded to Dr. Tompkins at the Massachusetts General Hospital, Boston, MA and in part, by research grants awarded to Dr. Herndon at the University of Texas Medical Branch, Galveston, TX, by the National Institute of General Medical Sciences (P50 GM-60338, R01 GM-56687, T32 GM-008256). Portions of the research were supported by a grant from the National Institutes of Health National Center for Research Resources (RR018522 and 5P41RR018522-10) and National Institute of General Medical Sciences (8 P41 GM103493-10). Dr. Finnerty is an ITS Career Development Scholar supported, in part, by NIH KL2RR029875 and NIH UL1RR029876. LC-MS proteomic analyses were performed in the Environmental Molecular Sciences Laboratory, a U.S. Department of Energy national scientific user facility located at the Pacific Northwest National Laboratory in Richland, WA. The Pacific Northwest National Laboratory is a multiprogram national laboratory operated by Battelle Memorial Institute for the U.S. Department of Energy under Contract DE-AC05-76RL01830.

The authors have not disclosed any potential conflicts of interest.

For information regarding this article, E-mail: ccfinner@utmb.edu

© 2013 by the Society of Critical Care Medicine and Lippincott Williams & Wilkins