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


Autoři: Stephanie C. Dreckmann aff001;  Saeid Amini-Nik aff001;  Ronald G. Tompkins aff003;  Miliana Vojvodic aff001;  Marc G. Jeschke aff001
Působiště autorů: Ross Tilley Burn Centre, Sunnybrook Health Sciences Centre, Department of Surgery, Toronto, ON, Canada aff001;  Division of Plastic Surgery, University of Toronto, Toronto, ON, Canada aff002;  Division of Surgery, Massachusetts General Hospital, Boston, MA, United States of America aff003;  Harvard Medical School, Boston, MA, United States of America aff004
Vyšlo v časopise: PLoS ONE 14(12)
Kategorie: Research Article
doi: 10.1371/journal.pone.0226425

Souhrn

Purpose

Mortality 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 methods

Microarray 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.

Results

Supervised 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).

Conclusions

The 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.

Klíčová slova:

Burn management – Burns – Elderly – Gene expression – Geriatric depression – Geriatrics – Immune response – Transcriptome analysis


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Článek vyšel v časopise

PLOS One


2019 Číslo 12