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

作者:Finnerty Celeste C*; Jeschke Marc G; Qian Wei Jun; Kaushal Amit; Xiao Wenzhong; Liu Tao; Gritsenko Marina A; Moore Ronald J; Camp David G II; Moldawer Lyle L; Elson Constance; Schoenfeld David; Gamelli Richard; Gibran Nicole; Klein Matthew; Arnoldo Brett; Remick Daniel; Smith Richard D; Davis Ronald; Tompkins Ronald G; Herndon David N
来源:Critical Care Medicine, 2013, 41(6): 1421-1434.
DOI:10.1097/CCM.0b013e31827c072e

摘要

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. %26lt;br%26gt;Design: Proteomic discovery study. %26lt;br%26gt;Setting: Five burn hospitals across the United States. %26lt;br%26gt;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. %26lt;br%26gt;Interventions: None. %26lt;br%26gt;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 beta 2-microglobulin correlated well with survival and may serve as clinical biomarkers. %26lt;br%26gt;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. (Crit Care Med 2013; 41: 1421-1434)

  • 出版日期2013-6