Distinct Transcriptome Signatures Associated With Mortality and Prolonged Recovery Following Burn Injury

A dysregulated immune response after severe burn injury is associated with detrimental short and long-term clinical outcomes. Key changes to gene expression within the first 24 h after burn injury have been identified, but longitudinal data is lacking. Therefore, this study aims to characterize gene expression during the first 3 weeks after burn injury and identify specific genes and pathways associated with distinct clinical outcomes. Patients presenting within 4 h of injury had blood RNA isolated for microarray gene expression at admission and set timepoints to 21 days. Inter- and intra-group comparisons were performed between 4 groups (G1 died within 7 days; G2 died after 7 days; G3 discharged after 7 days; and G4 discharged within 7 days). A total of 17 289 transcripts were quantified from 116 patients. At admission, there were 110, 80, and 31 differentially expressed genes in G1, G2, and G3, respectively, compared to G4, and were largely nonoverlapping. Longitudinal intra-group analyses also showed distinct group- and time-dependent patterns. Upregulation of genes and pathways related to the innate immune response and unfolded protein response predominated during early time points, while persistent upregulation of coagulation pathways and downregulation of immune-related pathways were identified days to weeks following injury. Overall, burn injury induces widespread transcriptomic responses, with larger and more sustained changes observed in patients with worse clinical outcomes. These gene expression signatures reveal underlying molecular mechanisms that occur immediately following injury and may have prognostic and diagnostic utility in the care of burn-injured patients.