The serum proteome of VA-ECMO patients changes over time and allows differentiation of survivors and non-survivors: an observational study.
Coagulation
Complement
ECMO
Inflammation
Mortality
Proteomics
Journal
Journal of translational medicine
ISSN: 1479-5876
Titre abrégé: J Transl Med
Pays: England
ID NLM: 101190741
Informations de publication
Date de publication:
12 05 2023
12 05 2023
Historique:
received:
03
03
2023
accepted:
30
04
2023
medline:
15
5
2023
pubmed:
13
5
2023
entrez:
12
5
2023
Statut:
epublish
Résumé
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is applied in patients with refractory hemodynamic failure. Exposure of blood components to high shear stress and the large extracorporeal surfaces in the ECMO circuit trigger a complex inflammatory response syndrome and coagulopathy which are believed to worsen the already poor prognosis of these patients. Mass spectrometry-based proteomics allow a detailed characterization of the serum proteome as it provides the identity and concentration of large numbers of individual proteins at the same time. In this study, we aimed to characterize the serum proteome of patients receiving VA-ECMO. Serum samples were collected on day 1 and day 3 after initiation of VA-ECMO. Samples underwent immunoaffinity based depletion for the 14 most abundant serum proteins, in-solution digestion and PreOmics clean-up. A spectral library was built with multiple measurements of a master-mix sample using variable mass windows. Individual samples were measured in data independent acquisition (DIA) mode. Raw files were analyzed by DIA-neural network. Unique proteins were log transformed and quantile normalized. Differential expression analysis was conducted with the LIMMA-R package. ROAST was applied to generate gene ontology enrichment analyses. Fourteen VA-ECMO patients and six healthy controls were recruited. Seven patients survived. Three hundred and fifty-one unique proteins were identified. One hundred and thirty-seven proteins were differentially expressed between VA-ECMO patients and controls. One hundred and forty-five proteins were differentially expressed on day 3 compared to day 1. Many of the differentially expressed proteins were involved in coagulation and the inflammatory response. The serum proteomes of survivors and non-survivors on day 3 differed from each other according to partial least-squares discriminant analysis (PLS-DA) and 48 proteins were differentially expressed. Many of these proteins have also been ascribed to processes in coagulation and inflammation (e.g., Factor IX, Protein-C, Kallikrein, SERPINA10, SEMA4B, Complement C3, Complement Factor D and MASP-1). The serum proteome of VA-ECMO patients displays major changes compared to controls and changes from day 1 until day 3. Many changes in the serum proteome are related to inflammation and coagulation. Survivors and non-survivors can be differentiated according to their serum proteomes using PLS-DA analysis on day 3. Our results build the basis for future studies using mass-spectrometry based serum proteomics as a tool to identify novel prognostic biomarkers. DRKS00011106.
Sections du résumé
BACKGROUND
Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) is applied in patients with refractory hemodynamic failure. Exposure of blood components to high shear stress and the large extracorporeal surfaces in the ECMO circuit trigger a complex inflammatory response syndrome and coagulopathy which are believed to worsen the already poor prognosis of these patients. Mass spectrometry-based proteomics allow a detailed characterization of the serum proteome as it provides the identity and concentration of large numbers of individual proteins at the same time. In this study, we aimed to characterize the serum proteome of patients receiving VA-ECMO.
METHODS
Serum samples were collected on day 1 and day 3 after initiation of VA-ECMO. Samples underwent immunoaffinity based depletion for the 14 most abundant serum proteins, in-solution digestion and PreOmics clean-up. A spectral library was built with multiple measurements of a master-mix sample using variable mass windows. Individual samples were measured in data independent acquisition (DIA) mode. Raw files were analyzed by DIA-neural network. Unique proteins were log transformed and quantile normalized. Differential expression analysis was conducted with the LIMMA-R package. ROAST was applied to generate gene ontology enrichment analyses.
RESULTS
Fourteen VA-ECMO patients and six healthy controls were recruited. Seven patients survived. Three hundred and fifty-one unique proteins were identified. One hundred and thirty-seven proteins were differentially expressed between VA-ECMO patients and controls. One hundred and forty-five proteins were differentially expressed on day 3 compared to day 1. Many of the differentially expressed proteins were involved in coagulation and the inflammatory response. The serum proteomes of survivors and non-survivors on day 3 differed from each other according to partial least-squares discriminant analysis (PLS-DA) and 48 proteins were differentially expressed. Many of these proteins have also been ascribed to processes in coagulation and inflammation (e.g., Factor IX, Protein-C, Kallikrein, SERPINA10, SEMA4B, Complement C3, Complement Factor D and MASP-1).
CONCLUSION
The serum proteome of VA-ECMO patients displays major changes compared to controls and changes from day 1 until day 3. Many changes in the serum proteome are related to inflammation and coagulation. Survivors and non-survivors can be differentiated according to their serum proteomes using PLS-DA analysis on day 3. Our results build the basis for future studies using mass-spectrometry based serum proteomics as a tool to identify novel prognostic biomarkers.
TRIAL REGISTRATION
DRKS00011106.
Identifiants
pubmed: 37173738
doi: 10.1186/s12967-023-04174-8
pii: 10.1186/s12967-023-04174-8
pmc: PMC10176307
doi:
Substances chimiques
Proteome
0
Banques de données
DRKS
['DRKS00011106']
Types de publication
Observational Study
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
319Informations de copyright
© 2023. The Author(s).
Références
Artif Organs. 2012 Jan;36(1):E1-20
pubmed: 22250822
J Cell Mol Med. 2020 Apr;24(8):4791-4803
pubmed: 32180339
Semin Cardiothorac Vasc Anesth. 2009 Sep;13(3):154-75
pubmed: 19767408
Bioinformatics. 2012 Jan 1;28(1):112-8
pubmed: 22039212
Front Physiol. 2021 Apr 27;12:652799
pubmed: 33995121
ACS Biomater Sci Eng. 2021 Sep 13;7(9):4402-4419
pubmed: 34436868
Endocrine. 2017 Oct;58(1):97-105
pubmed: 28822077
Crit Care. 2021 Jan 6;25(1):9
pubmed: 33407728
Resuscitation. 2017 Mar;112:34-40
pubmed: 27993632
J Proteome Res. 2020 Nov 6;19(11):4417-4427
pubmed: 32786691
Nat Methods. 2020 Jan;17(1):41-44
pubmed: 31768060
Semin Thromb Hemost. 2018 Feb;44(1):20-29
pubmed: 28898902
J Thromb Haemost. 2005 Apr;3(4):692-4
pubmed: 15842354
Bioinformatics. 2010 Sep 1;26(17):2176-82
pubmed: 20610611
Semin Immunol. 2016 Jun;28(3):268-77
pubmed: 27211838
Circulation. 2019 Dec 10;140(24):2019-2037
pubmed: 31815538
Biomater Adv. 2022 Aug;139:213014
pubmed: 35882160
EMBO Mol Med. 2021 Aug 9;13(8):e14167
pubmed: 34232570
Mol Syst Biol. 2017 Sep 26;13(9):942
pubmed: 28951502
Crit Care. 2016 Nov 28;20(1):387
pubmed: 27890016
Crit Care Med. 2020 Feb;48(2):167-175
pubmed: 31939784
Mediators Inflamm. 2002 Apr;11(2):69-73
pubmed: 12061426
N Engl J Med. 1999 Feb 11;340(6):448-54
pubmed: 9971870
Neoplasia. 2023 Feb;36:100871
pubmed: 36610378
J Immunother Cancer. 2022 Mar;10(3):
pubmed: 35347071
Pediatr Res. 2000 Nov;48(5):679-84
pubmed: 11044491
Biochim Biophys Acta. 2000 Jul 14;1480(1-2):235-44
pubmed: 11004567
J Intern Med. 2014 Oct;276(4):311-35
pubmed: 24661570
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
J Immunol Methods. 2014 Jan 31;403(1-2):26-36
pubmed: 24287423
Eur Heart J. 2019 Aug 21;40(32):2684-2694
pubmed: 31204432
Crit Care Explor. 2021 Sep 07;3(9):e0528
pubmed: 34514425
Sci Rep. 2018 Jun 15;8(1):9209
pubmed: 29907817
ASAIO J. 2019 Jan;65(1):77-83
pubmed: 29324513
Front Cardiovasc Med. 2019 Aug 08;6:114
pubmed: 31440518
J Thromb Thrombolysis. 2022 Apr;53(3):712-721
pubmed: 34529213
J Clin Invest. 1996 Sep 1;98(5):1081-7
pubmed: 8787668
Front Cardiovasc Med. 2021 Jul 19;8:689218
pubmed: 34350217
J Pediatr. 1996 May;128(5 Pt 1):670-8
pubmed: 8627440
Nat Immunol. 2016 Apr;17(4):406-13
pubmed: 26950237
J Proteome Res. 2010 May 7;9(5):2347-57
pubmed: 20302328
Hamostaseologie. 2020 Jun;40(2):221-225
pubmed: 32455462
J Surg Res. 2020 Feb;246:83-92
pubmed: 31562990
Clin Proteomics. 2022 May 24;19(1):18
pubmed: 35610567
Crit Care. 2017 Jun 22;21(1):157
pubmed: 28637497
Cell Syst. 2016 Mar 23;2(3):185-95
pubmed: 27135364
J Transl Med. 2022 May 23;20(1):238
pubmed: 35606879