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Critical Care Medicine:
doi: 10.1097/CCM.0b013e31827c072e
Clinical Investigations

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; for the Investigators of the Inflammation and the Host Response Glue Grant

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Abstract

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.

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

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