Noninvasive proteomic biomarkers for alcohol-related liver disease.

Autor: Niu L; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Thiele M; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark.; Department of Clinical Research, University of Southern Denmark, Odense, Denmark., Geyer PE; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.; OmicEra Diagnostics, Planegg, Germany., Rasmussen DN; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark., Webel HE; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Santos A; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK., Gupta R; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Pfizer Worldwide Research and Development, San Diego, CA, USA., Meier F; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany.; Functional Proteomics, Jena University Hospital, Jena, Germany., Strauss M; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany., Kjaergaard M; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark., Lindvig K; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark., Jacobsen S; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark., Rasmussen S; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Hansen T; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Krag A; Odense Liver Research Centre, Department of Gastroenterology and Hepatology, Odense University Hospital, Odense, Denmark., Mann M; Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mmann@biochem.mpg.de.; Department of Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Martinsried, Germany. mmann@biochem.mpg.de.
Jazyk: angličtina
Zdroj: Nature medicine [Nat Med] 2022 Jun; Vol. 28 (6), pp. 1277-1287. Date of Electronic Publication: 2022 Jun 02.
DOI: 10.1038/s41591-022-01850-y
Abstrakt: Alcohol-related liver disease (ALD) is a major cause of liver-related death worldwide, yet understanding of the three key pathological features of the disease-fibrosis, inflammation and steatosis-remains incomplete. Here, we present a paired liver-plasma proteomics approach to infer molecular pathophysiology and to explore the diagnostic and prognostic capability of plasma proteomics in 596 individuals (137 controls and 459 individuals with ALD), 360 of whom had biopsy-based histological assessment. We analyzed all plasma samples and 79 liver biopsies using a mass spectrometry (MS)-based proteomics workflow with short gradient times and an enhanced, data-independent acquisition scheme in only 3 weeks of measurement time. In plasma and liver biopsy tissues, metabolic functions were downregulated whereas fibrosis-associated signaling and immune responses were upregulated. Machine learning models identified proteomics biomarker panels that detected significant fibrosis (receiver operating characteristic-area under the curve (ROC-AUC), 0.92, accuracy, 0.82) and mild inflammation (ROC-AUC, 0.87, accuracy, 0.79) more accurately than existing clinical assays (DeLong's test, P < 0.05). These biomarker panels were found to be accurate in prediction of future liver-related events and all-cause mortality, with a Harrell's C-index of 0.90 and 0.79, respectively. An independent validation cohort reproduced the diagnostic model performance, laying the foundation for routine MS-based liver disease testing.
(© 2022. The Author(s).)
Databáze: MEDLINE
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