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1. Department of Burns and Plastic Surgery
2. Medical University
3. Department of Burns and Plastic Surgery, Affiliated Huaian No.1 People’s Hospital of Nanjing Medical University
4. Department of Burns and Plastic Surgery, Affiliated Hospital of Nantong University
5. Department of Burns and Plastic Surgery, Northern Jiangsu People’s Hospital
6. Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangsu University
7. Department of Burns and Plastic Surgery, Affiliated Hospital of Jiangnan University
纸质出版日期:2023,
网络出版日期:2023-1-15,
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Jiamin Huang, Yi Chen, Zaiwen Guo, 等. Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis[J]. Burns & Trauma, 2023,11(1).
Jiamin Huang, Yi Chen, Zaiwen Guo, Yanzhen Yu, Yi Zhang, Pingsong Li, Lei Shi, Guozhong Lv, Bingwei Sun, Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis, Burns & Trauma, Volume 11, 2023, tkac050, https://doi.org/10.1093/burnst/tkac050
Jiamin Huang, Yi Chen, Zaiwen Guo, 等. Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis[J]. Burns & Trauma, 2023,11(1). DOI: 10.1093/burnst/tkac050.
Jiamin Huang, Yi Chen, Zaiwen Guo, Yanzhen Yu, Yi Zhang, Pingsong Li, Lei Shi, Guozhong Lv, Bingwei Sun, Prospective study and validation of early warning marker discovery based on integrating multi-omics analysis in severe burn patients with sepsis, Burns & Trauma, Volume 11, 2023, tkac050, https://doi.org/10.1093/burnst/tkac050 DOI:
BackgroundEarly detection
timely diagnosis and rapid response are essential for case management and precautions of burn-associated sepsis. However
studies on indicators for early warning and intervention have rarely been conducted. This study was performed to better understand the pathophysiological changes and targets for prevention of severe burn injuries.MethodsWe conducted a multi-center
prospective multi-omics study
including genomics
microRNAomics
proteomics and single-cell transcriptomics
in 60 patients with severe burn injuries. A mouse model of severe burn injuries was also constructed to verify the early warning ability and therapeutic effects of potential markers.ResultsThrough genomic analysis
we identified seven important susceptibility genes (DNAH11
LAMA2
ABCA2
ZFAND4
CEP290
MUC20 and ENTPD1) in patients with severe burn injuries complicated with sepsis. Through plasma miRNAomics studies
we identified four miRNAs (hsa-miR-16-5p
hsa-miR-185-5p
hsa-miR-451a and hsa-miR-423-5p) that may serve as early warning markers of burn-associated sepsis. A proteomic study indicated the changes in abundance of major proteins at different time points after severe burn injury and revealed the candidate early warning markers S100A8 and SERPINA10. In addition
the proteomic analysis indicated that neutrophils play an important role in the pathogenesis of severe burn injuries
as also supported by findings from single-cell transcriptome sequencing of neutrophils. Through further studies on severely burned mice
we determined that S100A8 is also a potential early therapeutic target for severe burn injuries
beyond being an early warning indicator.ConclusionsOur multi-omics study identified seven susceptibility genes
four miRNAs and two proteins as early warning markers for severe burn-associated sepsis. In severe burn-associated sepsis
the protein S100A8 has both warning and therapeutic effects.
Early warningMarkerIntegrating multi-omics analysisSevere burnSepsis
1.James SL, Lucchesi LR, Bisignano C, Castle CD, Dingels ZV, Fox JT, et al. Epidemiology of injuries from fire, heat and hot substances: global, regional and national morbidity and mortality estimates from the global burden of disease 2017 study. Inj Prev. 2020;26:i36–36i45.
2.Snell JA, Loh NH, Mahambrey T, Shokrollahi K. Clinical review: the critical care management of the burn patient. Crit Care. 2013;17:241.
3.Guo HF, Abd Hamid R, Mohd Ali R, Chang SK, Rahman MH, Zainal Z, et al. Healing properties of epidermal growth factor and Tocotrienol-rich fraction in deep partial-thickness experimental burn wounds. Antioxidants (Basel). 2020;9: 130.
4.Williams FN, Herndon DN, Hawkins HK, Lee JO, Cox RA, Kulp GA, et al. The leading causes of death after burn injury in a single pediatric burn center. Crit Care. 2009;13:R183.
5.Beckmann N, Huber F, Hanschen M, St Pierre Schneider B, Nomellini V, Caldwell CC. Scald injury-induced T cell dysfunction can be mitigated by Gr1(+) cell depletion and blockage of CD47/CD172a Signaling. Front Immunol. 2020;11:876.
6.Shi C, Wang X, Wang L, Meng Q, Guo D, Chen L, et al. A nanotrap improves survival in severe sepsis by attenuating hyperinflammation. Nat Commun. 2020;11:3384.
7.Li J, Kong P, Chen C, Tang J, Jin X, Yan J, et al. Targeting IL-17A improves the Dysmotility of the small intestine and alleviates the injury of the interstitial cells of Cajal during sepsis. Oxidative Med Cell Longev. 2019;2019:1–15.
8.Knox DB, Lanspa MJ, Kuttler KG, Brewer SC, Brown SM. Phenotypic clusters within sepsis-associated multiple organ dysfunction syndrome. Intensive Care Med. 2015;41:814–22.
9.Greenhalgh DG. Sepsis in the burn patient: a different problem than sepsis in the general population. Burns Trauma. 2017;5:23.
10.Soedjana H, Nadia J, Sundoro A, Hasibuan L, Rubianti IW, Putri AC, et al. The profile of severe burn injury patients with sepsis in Hasan Sadikin Bandung general HospitaL. Ann Burns Fire Disasters. 2020;33:312–6.
11.Vono M, Lin A, Norrby-Teglund A, Koup RA, Liang F, Loré K. Neutrophils acquire the capacity for antigen presentation to memory CD4(+) T cells in vitro and ex vivo. Blood. 2017;129:1991–2001.
12.Opal SM. Endotoxins and other sepsis triggers. Contrib Nephrol. 2010;167:14–24.
13.Wittayachamnankul B, Chentanakij B, Sruamsiri K, Chattipakorn N. The role of central venous oxygen saturation, blood lactate, and central venous-to-arterial carbon dioxide partial pressure difference as a goal and prognosis of sepsis treatment. J Crit Care. 2016;36:223–9.
14.Tan M, Lu Y, Jiang H, Zhang L. The diagnostic accuracy of procalcitonin and C-reactive protein for sepsis: a systematic review and meta-analysis. J Cell Biochem. 2019;120:5852–9.
15.Ruangsomboon O, Panjaikaew P, Monsomboon A, Chakorn T, Permpikul C, Limsuwat C. Diagnostic and prognostic utility of presepsin for sepsis in very elderly patients in the emergency department. Clin Chim Acta. 2020;510:723–32.
16.Li X, Gong W, Wang H, Li T, Attri KS, Lewis RE, et al. O-GlcNAc transferase suppresses inflammation and necroptosis by targeting receptor-interacting serine/threonine-protein kinase 3. Immunity. 2019;50:576–90.e6.
17.Zhang F, Qi L, Feng Q, Zhang B, Li X, Liu C, et al. HIPK2 phosphorylates HDAC3 for NF-κB acetylation to ameliorate colitis-associated colorectal carcinoma and sepsis. Proc Natl Acad Sci U S A. 2021;118.
18.Teng G, Papavasiliou FN. Immunoglobulin somatic hypermutation. Annu Rev Genet. 2007;41:107–20.
19.Hanczko R, Fernandez DR, Doherty E, Qian Y, Vas G, Niland B, et al. Prevention of hepatocarcinogenesis and increased susceptibility to acetaminophen-induced liver failure in transaldolase-deficient mice by N-acetylcysteine. J Clin Invest. 2009;119:1546–57.
20.Schroeder HW, Jr, Cavacini L. Structure and function of immunoglobulins. J Allergy Clin Immunol. 2010;125:S41–52.
21.McHeyzer-Williams M, Okitsu S, Wang N, McHeyzer-Williams L. Molecular programming of B cell memory. Nat Rev Immunol. 2011;12:24–34.
22.Su Y, Shen J, Gao L, Tian H, Tian Z, Qin W. Molecular interactions of re-released proteins in electrophoresis of human erythrocytes. Electrophoresis. 2012;33:1402–5.
23.Lefranc MP. Immunoglobulin and T cell receptor genes: IMGT(®) and the birth and rise of Immunoinformatics. Front Immunol. 2014;5:22.
24.Koymans KJ, Bisschop A, Vughs MM, van Kessel KP, de Haas CJ, van Strijp JA. Staphylococcal Superantigen-like protein 1 and 5 (SSL1 & SSL5) limit neutrophil chemotaxis and migration through MMP-inhibition. Int J Mol Sci. 2016;17.
25.Chhunchha B, Kubo E, Singh P, Singh DP. Sumoylation-deficient Prdx6 repairs aberrant Sumoylation-mediated Sp1 dysregulation-dependent Prdx6 repression and cell injury in aging and oxidative stress. Aging (Albany NY). 2018;10:2284–315.
26.Shabani F, Farasat A, Mahdavi M, Gheibi N. Calprotectin (S100A8/S100A9): a key protein between inflammation and cancer. Inflamm Res. 2018;67:801–12.
27.Francis A, Bosio E, Stone SF, Fatovich DM, Arendts G, MacDonald S, et al. Markers involved in innate immunity and neutrophil activation are elevated during acute human anaphylaxis: validation of a microarray study. J Innate Immun. 2019;11:63–73.
28.Leite G, Scicluna BP, van der Poll T, Salomão R. Genetic signature related to heme-hemoglobin metabolism pathway in sepsis secondary to pneumonia. NPJ Syst Biol Appl. 2019;5:26.
29.Wu Y, Zeng J, Roscoe BP, Liu P, Yao Q, Lazzarotto CR, et al. Highly efficient therapeutic gene editing of human hematopoietic stem cells. Nat Med. 2019;25:776–83.
30.Jing M, Han G, Wan J, Zhang S, Yang J, Zong W, et al. Catalase and superoxide dismutase response and the underlying molecular mechanism for naphthalene. Sci Total Environ. 2020;736:139567.
31.Wang X, Xiong H, Liang D, Chen Z, Li X, Zhang K. The role of SRGN in the survival and immune infiltrates of skin cutaneous melanoma (SKCM) and SKCM-metastasis patients. BMC Cancer. 2020;20:378.
32.Eleutherio E, Silva Magalhães RS, de Araújo BA, Monteiro Neto JR, de Holanda Paranhos L. SOD1, more than just an antioxidant. Arch Biochem Biophys. 2021;697:108701.
33.Gilmartin AG, Groy A, Gore ER, Atkins C, Long ER, Montoute MN, et al. In vitro and in vivo induction of fetal hemoglobin with a reversible and selective DNMT1 inhibitor. Haematologica. 2021;106:1979–87.
34.Vandooren J, Pereira R, Ugarte-Berzal E, Rybakin V, Noppen S, Stas MR, et al. Internal Disulfide bonding and glycosylation of Interleukin-7 protect against proteolytic inactivation by neutrophil Metalloproteinases and serine proteases. Front Immunol. 2021;12:701739.
35.Zhang Q, Hu Y, Hu JE, Ding Y, Shen Y, Xu H, et al. Sp1-mediated upregulation of Prdx6 expression prevents podocyte injury in diabetic nephropathy via mitigation of oxidative stress and ferroptosis. Life Sci. 2021;278:119529.
36.Huang J, Zhu Z, Ji D, Sun R, Yang Y, Liu L, et al. Single-cell transcriptome profiling reveals neutrophil heterogeneity and functional multiplicity in the early stage of severe burn patients. Front Immunol. 2021;12:792122.
37.Manning J. Sepsis in the burn patient. Crit Care Nurs Clin North Am. 2018;30:423–30.
38.D'Abbondanza JA, Shahrokhi S. Burn infection and burn sepsis. Surg Infect. 2021;22:58–64.
39.Savio L, de Andrade MP, Figliuolo VR, de Avelar Almeida TF, Santana PT, Oliveira S, et al. CD39 limits P2X7 receptor inflammatory signaling and attenuates sepsis-induced liver injury. J Hepatol. 2017;67:716–26.
40.Yang M, Lu L, Kang Z, Ma T, Wang Y. Overexpressed CD39 mitigates sepsis-induced kidney epithelial cell injury via suppressing the activation of NLR family pyrin domain containing 3. Int J Mol Med. 2019;44:1707–18.
41.Cohen HB, Briggs KT, Marino JP, Ravid K, Robson SC, Mosser DM. TLR stimulation initiates a CD39-based autoregulatory mechanism that limits macrophage inflammatory responses. Blood. 2013;122:1935–45.
42.Imai M, Goepfert C, Kaczmarek E, Robson SC. CD39 modulates IL-1 release from activated endothelial cells. Biochem Biophys Res Commun. 2000;270:272–8.
43.Leikauf GD, Concel VJ, Bein K, Liu P, Berndt A, Martin TM, et al. Functional genomic assessment of phosgene-induced acute lung injury in mice. Am J Respir Cell Mol Biol. 2013;49:368–83.
44.Thavarajah T, Dos Santos CC, Slutsky AS, Marshall JC, Bowden P, Romaschin A, et al. The plasma peptides of sepsis. Clin Proteomics. 2020;17:26.
45.Li Z, Zeppa JJ, Hancock MA, McCormick JK, Doherty TM, Hendy GN, et al. Staphylococcal Superantigens use LAMA2 as a Coreceptor to activate T cells. J Immunol. 2018;200:1471–9.
46.Zhang Z, Chen L, Xu P, Xing L, Hong Y, Chen P. Gene correlation network analysis to identify regulatory factors in sepsis. J Transl Med. 2020;18:381.
47.Casabonne D, Benavente Y, Seifert J, Costas L, Armesto M, Arestin M, et al. Serum levels of hsa-miR-16-5p, hsa-miR-29a-3p, hsa-miR-150-5p, hsa-miR-155-5p and hsa-miR-223-3p and subsequent risk of chronic lymphocytic leukemia in the EPIC study. Int J Cancer. 2020;147:1315–24.
48.Bohatá J, Horváthová V, Pavlíková M, Stibůrková B. Circulating microRNA alternations in primary hyperuricemia and gout. Arthritis Res Ther. 2021;23:186.
49.Tejiram S, Romanowski KS, Palmieri TL. Initial management of severe burn injury. Curr Opin Crit Care. 2019;25:647–52.
50.Jeschke MG, van Baar ME, Choudhry MA, Chung KK, Gibran NS, Logsetty S. Burn injury. Nat Rev Dis Primers. 2020;6:11.
51.Liu L, Shao Y, Zhang Y, Yang Y, Huang J, Li L, et al. Neutrophil-derived heparin binding protein triggers vascular leakage and synergizes with myeloperoxidase at the early stage of severe burns (with video). Burns Trauma. 2021;9:tkab030.
52.Li Y, Chen B, Yang X, Zhang C, Jiao Y, Li P, et al. S100a8/a9 Signaling causes mitochondrial dysfunction and Cardiomyocyte death in response to ischemic/reperfusion injury. Circulation. 2019;140:751–64.
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