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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: https://doi.org/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


Zdroje

1. Association AB. National burn repository. 2016 Natl Burn Repos. 2016;

2. Forjuoh SN. Burns in low- and middle-income countries: a review of available literature on descriptive epidemiology, risk factors, treatment, and prevention. Burns [Internet]. 2006 Aug [cited 2019 Feb 20];32(5):529–37. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0305417906001203 doi: 10.1016/j.burns.2006.04.002 16777340

3. Kraft R, Herndon DN, Al-Mousawi AM, Williams FN, Finnerty CC, Jeschke MG. Burn size and survival probability in paediatric patients in modern burn care: a prospective observational cohort study. Lancet [Internet]. 2012 Mar [cited 2018 Dec 11];379(9820):1013–21. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0140673611613457 doi: 10.1016/S0140-6736(11)61345-7 22296810

4. Herndon DN. Total Burn Care. Total Burn Care. 2007.

5. Jeschke MG, Patsouris D, Stanojcic M, Abdullahi A, Rehou S, Pinto R, et al. Pathophysiologic Response to Burns in the Elderly ☆. EBIOM. 2015;

6. Jeschke MG, Pinto R, Costford SR, Amini-Nik S. Threshold age and burn size associated with poor outcomes in the elderly after burn injury. Burns. 2016;

7. Pereira CT, Barrow RE, Sterns AM, Hawkins HK, Kimbrough CW, Jeschke MG, et al. Age-Dependent Differences in Survival after Severe Burns: A Unicentric Review of 1,674 Patients and 179 Autopsies over 15 Years. J Am Coll Surg [Internet]. 2006 Mar 1 [cited 2018 Dec 11];202(3):536–48. Available from: http://linkinghub.elsevier.com/retrieve/pii/S1072751505017424 doi: 10.1016/j.jamcollsurg.2005.11.002 16500259

8. Murray CJL, Lopez AD, Harvard School of Public Health. WH, World Health Organization. W, World Bank. HS of P. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020 [Internet]. Published by the Harvard School of Public Health on behalf of the World Health Organization and the World Bank; 1996 [cited 2019 Feb 20]. 990 p. Available from: https://apps.who.int/iris/handle/10665/41842

9. Stanojcic M, Chen P, Xiu F, Jeschke MG. Impaired Immune Response in Elderly Burn Patients. Ann Surg [Internet]. 2016 Jul [cited 2019 Mar 2];264(1):195–202. Available from: http://www.ncbi.nlm.nih.gov/pubmed/26649579 doi: 10.1097/SLA.0000000000001408 26649579

10. Lundgren RS, Kramer CB, Rivara FP, Wang J, Heimbach DM, Gibran NS, et al. Influence of Comorbidities and Age on Outcome Following Burn Injury in Older Adults. J Burn Care Res [Internet]. 2009 Mar [cited 2019 Mar 2];30(2):307–14. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19165104 doi: 10.1097/BCR.0b013e318198a416 19165104

11. Albornoz CR, Villegas J, Sylvester M, Peña V, Bravo I. Burns are more aggressive in the elderly: Proportion of deep burn area/total burn area might have a role in mortality. Burns [Internet]. 2011 Sep [cited 2019 Mar 2];37(6):1058–61. Available from: http://www.ncbi.nlm.nih.gov/pubmed/21571438 doi: 10.1016/j.burns.2011.03.006 21571438

12. Gerstein AD, Phillips TJ, Rogers GS, Gilchrest BA. Wound Healing and Aging. Dermatol Clin [Internet]. 1993 Oct 1 [cited 2018 Dec 11];11(4):749–57. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0733863518302274 8222358

13. Pham TN, Kramer CB, Wang J, Rivara FP, Heimbach DM, Gibran NS, et al. Epidemiology and outcomes of older adults with burn injury: an analysis of the National Burn Repository. J Burn Care Res [Internet]. 2009 [cited 2018 Dec 11];30(1):30–6. Available from: http://www.ncbi.nlm.nih.gov/pubmed/19060727 doi: 10.1097/BCR.0b013e3181921efc 19060727

14. Rehou S, Shahrokhi S, Thai J, Stanojcic M, Jeschke MG. Acute Phase Response in Critically Ill Elderly Burn Patients. Crit Care Med [Internet]. 2019 Feb [cited 2019 Mar 2];47(2):201–9. Available from: http://insights.ovid.com/crossref?an=00003246-201902000-00008 doi: 10.1097/CCM.0000000000003516 30371519

15. Inflammation and the Host Response to Injury [Internet]. [cited 2018 Dec 11]. Available from: http://www.gluegrant.org/

16. Silver GM, Klein MB, Herndon DN, Gamelli RL, Gibran NS, Altstein L, et al. Standard operating procedures for the clinical management of patients enrolled in a prospective study of inflammation and the host response to thermal injury. J Burn Care Res. 2007;

17. Calvano SE, Xiao W, Richards DR, Felciano RM, Baker H V., Cho RJ, et al. A network-based analysis of systemic inflammation in humans. Nature. 2005;

18. Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, et al. Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci. 2005;

19. Merico D, Isserlin R, Stueker O, Emili A, Bader GD. Enrichment map: A network-based method for gene-set enrichment visualization and interpretation. PLoS One. 2010;

20. AmiGO 2: Welcome [Internet]. [cited 2016 Feb 1]. Available from: http://amigo.geneontology.org/amigo

21. KEGG PATHWAY Database [Internet]. [cited 2016 Feb 1]. Available from: https://www.genome.jp/kegg/pathway.html#organismal

22. Reactome Pathways [Internet]. [cited 2016 Feb 1]. Available from: https://www.reactome.org/download/current/ReactomePathwaysRelation.txt

23. Robinson H, Monafo WW, Saver SM, Gallagher N 1. The Role of Erythropoietin in the Anemia of Thermal Injury. Ann Surg [Internet]. 1973 [cited 2018 Dec 11];178(5):565–72. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1355733/pdf/annsurg00249-0006.pdf doi: 10.1097/00000658-197311000-00002 4795883

24. Sood RF, Gibran NS, Arnoldo BD, Gamelli RL, Herndon DN, Tompkins RG. Early leukocyte gene expression associated with age, burn size, and inhalation injury in severely burned adults. J Trauma Acute Care Surg. 2016;

25. Yan S, Tsurumi A, Que YA, Ryan CM, Bandyopadhaya A, Morgan AA, et al. Prediction of multiple infections after severe burn trauma: A prospective cohort study. Ann Surg. 2015;

26. Gao Y, Nai W, Yang L, Lu Z, Shi P, Jin H, et al. Construction of an immunorelated protein-protein interaction network for clarifying the mechanism of burn. Burns. 2016;

27. Farinas AF, Bamba R, Pollins AC, Cardwell NL, Nanney LB, Thayer WP. Burn wounds in the young versus the aged patient display differential immunological responses. Burns. 2018;

28. Baeuerle PA, Henkel T. Function and Activation of NF-kappaB in the Immune System. Annu Rev Immunol. 1994;

29. Rager JE. The Role of Apoptosis-Associated Pathways as Responders to Contaminants and in Disease Progression. Syst Biol Toxicol Environ Heal [Internet]. 2015 Jan 1 [cited 2018 Dec 11];187–205. Available from: https://www.sciencedirect.com/science/article/pii/B9780128015643000080

30. Sen P, Shah PP, Nativio R, Berger SL. Epigenetic Mechanisms of Longevity and Aging. Cell. 2016.

31. Boule LA, Kovacs EJ. Alcohol, aging, and innate immunity. J Leukoc Biol [Internet]. 2017 Jul 1 [cited 2019 Jun 27];102(1):41–55. Available from: http://doi.wiley.com/10.1189/jlb.4RU1016-450R 28522597

32. Howland J, Hingson R. Alcohol as a risk factor for injuries or death due to fires and burns: review of the literature. Public Health Rep [Internet]. 1987 [cited 2019 Jun 27];102(5):475–83. Available from: http://www.ncbi.nlm.nih.gov/pubmed/3116577 3116577


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