Determination of burn patient outcome by large-scale quantitative discovery proteomics

Crit Care Med. 2013 Jun;41(6):1421-34. doi: 10.1097/CCM.0b013e31827c072e.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers
  • Blood Proteins / analysis*
  • Blood Proteins / metabolism
  • Burn Units
  • Burns / blood*
  • Burns / diagnosis
  • Burns / mortality*
  • Cytokines / blood*
  • Cytokines / metabolism
  • Female
  • Humans
  • Inflammation Mediators / blood*
  • Inflammation Mediators / metabolism
  • Male
  • Mass Spectrometry
  • Middle Aged
  • Prognosis
  • Proteome / metabolism
  • Proteomics / methods*

Substances

  • Biomarkers
  • Blood Proteins
  • Cytokines
  • Inflammation Mediators
  • Proteome