Plasma Proteome Response to Severe Burn Injury Revealed by O-18-Labeled "Universal" Reference-Based Quantitative Proteomics

Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, Washington 99352, USA.
Journal of Proteome Research (Impact Factor: 4.25). 09/2010; 9(9):4779-89. DOI: 10.1021/pr1005026
Source: PubMed


A burn injury represents one of the most severe forms of human trauma and is responsible for significant mortality worldwide. Here, we present the first quantitative proteomics investigation of the blood plasma proteome response to severe burn injury by comparing the plasma protein concentrations of 10 healthy control subjects with those of 15 severe burn patients at two time-points following the injury. The overall analytical strategy for this work integrated immunoaffinity depletion of the 12 most abundant plasma proteins with cysteinyl-peptide enrichment-based fractionation prior to LC-MS analyses of individual patient samples. Incorporation of an 18O-labeled "universal" reference among the sample sets enabled precise relative quantification across samples. In total, 313 plasma proteins confidently identified with two or more unique peptides were quantified. Following statistical analysis, 110 proteins exhibited significant abundance changes in response to the burn injury. The observed changes in protein concentrations suggest significant inflammatory and hypermetabolic response to the injury, which is supported by the fact that many of the identified proteins are associated with acute phase response signaling, the complement system, and coagulation system pathways. The regulation of approximately 35 proteins observed in this study is in agreement with previous results reported for inflammatory or burn response, but approximately 50 potentially novel proteins previously not known to be associated with burn response or inflammation are also found. Elucidating proteins involved in the response to severe burn injury may reveal novel targets for therapeutic interventions as well as potential predictive biomarkers for patient outcomes such as multiple organ failure.

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Available from: Celeste Finnerty, Jun 20, 2014
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    • "The growing number of these studies has resulted in a " data deluge [46]. " Researchers are being overwhelmed by data in large part because the methods of choice for analysis of these data are invariably based on statistical associations [47] [48] [49] [50] [51] [52] [53] [54]. Such analyses may suggest principal drivers of inflammation and MODS [54] [55] and may define the interconnected networks of mediators and signaling responses that underlie the pathobiology of acute critical illness [56] [57]. "
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    • "Our interest was to find the proteins whose abundances were different between these two recovery groups. Samples were prepared using 18 O-labeled universal reference-based approach described in Qian et al. (2010) and analyzed by MS. Each experiment contained peptides from a pool sample and from an individual patient sample. "
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    • "There have been notable successes in this approach, which has led to the possibility of better defining the dynamic patient state. Various studies have shed mechanistic insights into the biology of trauma and sepsis based on DNA microarray (including the landmark first study from the Trauma and the Host Response to Injury " Glue " grant and studies in several countries identifying signature responses of sepsis, trauma, and burn patients) [6] [17] [18] [19] [20] [21]; plasma proteomics in similar patients [22] [23]; and the use of signal processing techniques, multivariate dynamic clustering, and machine-learning algorithms based on physiologic measurements and inflammation biomarkers [24] [25] [26] [27] [28]. Furthermore, " omics " studies and data-driven computational analyses in animal models of trauma/hemorrhage, burns, and sepsis have both verified the importance of known biological pathways and suggested some novel ones [29] [30] [31]. "
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