Cargando…

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

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 unkn...

Descripción completa

Detalles Bibliográficos
Autores principales: Dreckmann, Stephanie C., Amini-Nik, Saeid, Tompkins, Ronald G., Vojvodic, Miliana, Jeschke, Marc G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910697/
https://www.ncbi.nlm.nih.gov/pubmed/31834907
http://dx.doi.org/10.1371/journal.pone.0226425
_version_ 1783479138964733952
author Dreckmann, Stephanie C.
Amini-Nik, Saeid
Tompkins, Ronald G.
Vojvodic, Miliana
Jeschke, Marc G.
author_facet Dreckmann, Stephanie C.
Amini-Nik, Saeid
Tompkins, Ronald G.
Vojvodic, Miliana
Jeschke, Marc G.
author_sort Dreckmann, Stephanie C.
collection PubMed
description 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.
format Online
Article
Text
id pubmed-6910697
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-69106972019-12-27 Genome-wide comparisons of gene expression in adult versus elderly burn patients Dreckmann, Stephanie C. Amini-Nik, Saeid Tompkins, Ronald G. Vojvodic, Miliana Jeschke, Marc G. PLoS One Research Article 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. Public Library of Science 2019-12-13 /pmc/articles/PMC6910697/ /pubmed/31834907 http://dx.doi.org/10.1371/journal.pone.0226425 Text en © 2019 Dreckmann et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Dreckmann, Stephanie C.
Amini-Nik, Saeid
Tompkins, Ronald G.
Vojvodic, Miliana
Jeschke, Marc G.
Genome-wide comparisons of gene expression in adult versus elderly burn patients
title Genome-wide comparisons of gene expression in adult versus elderly burn patients
title_full Genome-wide comparisons of gene expression in adult versus elderly burn patients
title_fullStr Genome-wide comparisons of gene expression in adult versus elderly burn patients
title_full_unstemmed Genome-wide comparisons of gene expression in adult versus elderly burn patients
title_short Genome-wide comparisons of gene expression in adult versus elderly burn patients
title_sort genome-wide comparisons of gene expression in adult versus elderly burn patients
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6910697/
https://www.ncbi.nlm.nih.gov/pubmed/31834907
http://dx.doi.org/10.1371/journal.pone.0226425
work_keys_str_mv AT dreckmannstephaniec genomewidecomparisonsofgeneexpressioninadultversuselderlyburnpatients
AT amininiksaeid genomewidecomparisonsofgeneexpressioninadultversuselderlyburnpatients
AT tompkinsronaldg genomewidecomparisonsofgeneexpressioninadultversuselderlyburnpatients
AT vojvodicmiliana genomewidecomparisonsofgeneexpressioninadultversuselderlyburnpatients
AT jeschkemarcg genomewidecomparisonsofgeneexpressioninadultversuselderlyburnpatients