Genome-wide Monocytic mRNA Expression in Polytrauma Patients for Identification of Clinical Outcome
Abstract:
Background: Immune activation in multiple trauma is closely linked to the development of multiple organ dysfunction and failure, and consequently, has a profound influence on patient outcome. Although peripheral blood monocytes play a critical role in this immune response, their genome-wide expression response immediately following traumatic injury has never been described.
Methods: Thirteen patients presenting with multiple blunt trauma were studied. Peripheral blood monocytes were obtained within 90 minutes and at six, 12, 24, 48 and 72 hours after trauma. A biotinylated cRNA target was hybridized to Affymetrix U133A microarrays.
Results: Supervised analysis identified 763 probe sets that were differentially expressed
(p<0.001) in patients who died (n=3) as compared those who survived (n=10). The ability of these probe sets to function as a classifier of dichotomous outcome was significantly demonstrated with six prediction models. Using pathway analysis, a network of proinflammatory genes and intracellular signalling pathways leading to c-Jun activation were consistently overexpressed in patients who died.
Conclusions: Genome-wide mRNA expression patterns in circulating peripheral blood monocytes from multiple injured patients can discriminate between clinical outcomes and provide unique insights into the reprioritization of gene expression by the host, as well as into potential initiating mechanisms which lead to irreversible multiple organ dysfunction and death.
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