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Published on: February 27, 2015
Determination of burn patient outcome by large-scale quantitative discovery proteomics
Celeste C Finnerty1, Marc G Jeschke, Wei-Jun Qian
1Department of Surgery, University of Texas Medical Branch, and Shriners Hospitals for Children, Galveston, TX, USA. ccfinner@utmb.edu
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.