O45 – Genomic and Proteomic Survival Biomarker Profiles in Severely Burned Children
Author(s):
Background: Following a severe burn injury, massive perturbations in the peripheral blood leukocyte genome and proteome occur. We have previously reported differential gene expression in severely burned children and adults. Abundance of proteins such as cytokines or acute phase proteins has been used to predict patient outcome and clinical course. Here we examine protein and gene expression in severely burned children to determine candidate proteins and genes for predicting patient outcome. Additionally we identify pathways that are implicated in the survival response due to significant differences in both gene and protein expression with respect to survival of the burn injury.
Hypothesis: Both genes and proteins can be used to develop a biomarker profile that can be used to predict early identification of survival in children with large burn injuries.
Methods: Gene expression in peripheral blood leukocytes from pediatric burn patients was measured using the Affymetrix HGU133 Plus 2.0 microarray. For this analysis, 254 gene chips were analyzed. These represented 101 pediatric patients with >30% of total body surface area burned, admitted to our burn unit within 72 hours of injury, and requiring at least one oepration. 58 analytes (cytokines, hormones, acute phase proteins, metabolic markers) were measured in the serum using techniques such as ELISA, nephelometry, and multi-plex analysis. T-tests were used to determine candidate biomarker genes. ANOVAs were used to identify candidate proteins. Significance was accepted at p<0.05.
Results: On the Affymetrix GeneChips, 14,489 probe sets were differentially expressed in survivors compared to non-survivors, p<0.05. Changes in gene expression were similar to the modulations seen with cytokines and acute phase reactants. In both the proteomic and genomic data sets, the most significant differences associated with survival were found within the signaling pathways induced by IL17, IL10, IL4, and IL5.
Conclusions: These results suggest that biomarker candidate proteins and genes which may enable improved prediction of patient outcome can be correlated with survival. Identification of signaling pathways via methods such as these may enable determination of mechanisms and therapeutic targets in patients not surviving major burn injuiry