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

Celeste Finnerty, Marc G. Jeschke, Wei Jun Qian, Amit Kaushal, Wenzhong Xiao, Tao Liu, Marina A. Gritsenko, Ronald J. Moore, David G. Camp, Lyle L. Moldawer, Constance Elson, David Schoenfeld, Richard Gamelli, Nicole Gibran, Matthew Klein, Brett Arnoldo, Daniel Remick, Richard D. Smith, Ronald Davis, Ronald G. TompkinsDavid Herndon

Research output: Contribution to journalArticle

30 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1421-1434
Number of pages14
JournalCritical Care Medicine
Volume41
Issue number6
DOIs
StatePublished - Jun 2013

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Proteomics
Biomarkers
Survival
Wounds and Injuries
Liquid Chromatography
Survivors
Chemokine CCL8
Mass Spectrometry
Acute-Phase Reaction
Chemokine CCL2
Body Surface Area
Proteome
Granulocyte-Macrophage Colony-Stimulating Factor
Interleukin-8
Burns
Critical Illness
Interleukin-4
Insulin Resistance
Proteins
Cytokines

Keywords

  • biomarker
  • burn
  • inflammation
  • liquid chromatographymass spectrometry
  • plasma proteins
  • proteomic profiling

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Determination of burn patient outcome by large-scale quantitative discovery proteomics. / Finnerty, Celeste; Jeschke, Marc G.; Qian, Wei Jun; Kaushal, Amit; Xiao, Wenzhong; Liu, Tao; Gritsenko, Marina A.; Moore, Ronald J.; Camp, David G.; 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.

In: Critical Care Medicine, Vol. 41, No. 6, 06.2013, p. 1421-1434.

Research output: Contribution to journalArticle

Finnerty, C, Jeschke, MG, Qian, WJ, Kaushal, A, Xiao, W, Liu, T, Gritsenko, MA, Moore, RJ, Camp, DG, Moldawer, LL, Elson, C, Schoenfeld, D, Gamelli, R, Gibran, N, Klein, M, Arnoldo, B, Remick, D, Smith, RD, Davis, R, Tompkins, RG & Herndon, D 2013, 'Determination of burn patient outcome by large-scale quantitative discovery proteomics', Critical Care Medicine, vol. 41, no. 6, pp. 1421-1434. https://doi.org/10.1097/CCM.0b013e31827c072e
Finnerty, Celeste ; Jeschke, Marc G. ; Qian, Wei Jun ; Kaushal, Amit ; Xiao, Wenzhong ; Liu, Tao ; Gritsenko, Marina A. ; Moore, Ronald J. ; Camp, David G. ; 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. / Determination of burn patient outcome by large-scale quantitative discovery proteomics. In: Critical Care Medicine. 2013 ; Vol. 41, No. 6. pp. 1421-1434.
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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.",
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AU - Jeschke, Marc G.

AU - Qian, Wei Jun

AU - Kaushal, Amit

AU - Xiao, Wenzhong

AU - Liu, Tao

AU - Gritsenko, Marina A.

AU - Moore, Ronald J.

AU - Camp, David G.

AU - Moldawer, Lyle L.

AU - Elson, Constance

AU - Schoenfeld, David

AU - Gamelli, Richard

AU - Gibran, Nicole

AU - Klein, Matthew

AU - Arnoldo, Brett

AU - Remick, Daniel

AU - Smith, Richard D.

AU - Davis, Ronald

AU - Tompkins, Ronald G.

AU - Herndon, David

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N2 - 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.

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KW - inflammation

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KW - plasma proteins

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