Genome-wide comparisons of gene expression in adult versus elderly burn patients

Abstract

PurposeMortality and morbidity rates of elderly burn patients remain high despite numerous advancements in modern burn care. While prior studies have offered first insights on the biochemical changes in elderly burn patients compared to adults, the underlying cellular responses remain largely unknown. In this study, we aim to characterize the transcriptome of elderly burn patients and compare it to adult burn patients to obtain insights into the underlying molecular responses post-burn and to elucidate the effect of advanced age on the acute burn response.Materials and methodsMicroarray data obtained from the Glue Grant Trauma-Related Database was obtained from blood specimens for ten elderly patients (n = 10), each with a set of two sex and total body surface area (TBSA) matched adult controls (n = 20), during the acute phase post-burn. Adult and elderly demographics and clinical outcomes were contrasted using using the Chi-Square test, Fisher’s Exact Test, or two-sample t-tests, as appropriate (p<0.05). Enrichment and heat maps were generated to compare gene expression in elderly versus adult burn patients.ResultsSupervised analysis identified multiple genes that were differentially expressed between the elderly and adult groups. Pathway analysis and heatmap generation suggest that elderly patients share a distinct hypo-inflammatory response in the acute post-burn phase with downregulation of a number of immune-related pathways, including those related to antigen processing, specifically via MHC class I, ubiquitination and proteasome degradation (p<0.001, FDR < .001). Cell signalling pathways, such as NF-κB, C-type lectin receptor, and T cell receptor signalling were also significantly downregulated in elderly burn patients, as well as those relating to antiviral immunity (p<0.001, FDR < .001). Many genes which were observed to be upregulated in elderly patients with high TBSA burn injuries were associated with destruction-related cellular pathways such as complement activation and immunoglobulin production (p<0.005, FDR <0.01).ConclusionsThe altered inflammatory and immune responses at the transcriptome level in elderly patients after burn are indicative of a failure in elderly burn patients to initiate an appropriate inflammatory and stress response during the acute phase post-burn.

Effect of Thermal Stimulation on Gene Expression Related to Skeletal Muscle-derived Cell Density

“…Severe burns include processes related to inflammation / immune system and cell activity, which are thought to be related to post-burn pathological processes [17]. A previous study [18] that examined gene expression in elderly burn patients reported that the expression of immune system signaling pathways was suppressed during the acute post-burn phase in pathway analysis. In this study, it is possible that no damage such as burns occurred to the cells.…”

Systemic immune response of burns from the acute to chronic phase

“…Since many of the genes whose expression was increased in elderly patients with severe burns were associated with cellular pathways associated with destruction, such as complement activation and immunoglobulin production, the altered inflammatory and immune responses in elderly patients after burn injury indicate that elderly burn patients are unable to initiate an appropriate inflammatory and stress response in the acute phase after burn injury. 55 The gene expression analysis of 213 burn patients and 79 healthy controls revealed that down‐regulated genes were enriched in the T‐cell activation pathway, while up‐regulated genes were enriched in the neutrophil activation response. Key genes that may be regulated by miRNAs (NFATC2, RORA, and CAMK4) were downregulated in burn patients.…”