Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia.

Autor:	Bech JM; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark; Sino-Danish Center for Education and Research, Aarhus University, Aarhus, Denmark., Terkelsen T; Center for Health Data Science, University of Copenhagen, Copenhagen, Denmark., Bartels AS; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Coscia F; Spatial Proteomics Group, Max-Delbrück-Centrum for Molecular Medicine in the Helmholtz Association, Berlin, Germany; Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Doll S; OmicEra Diagnostics GmbH, Planegg, Germany., Zhao S; Beijing Institute of Genomics, China National Center for Bioinformation, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China., Zhang Z; Beijing Institute of Genomics, China National Center for Bioinformation, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China., Brünner N; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark., Lindebjerg J; Department of Pathology, Lillebaelt Hospital, Vejle Hospital, Vejle, Denmark., Madsen GI; Department of Pathology, Odense University Hospital, Odense, Denmark., Fang X; Beijing Institute of Genomics, China National Center for Bioinformation, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Beijing, China., Mann M; Proteomics Program, Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark., Afonso Moreira JM; Department of Drug Design and Pharmacology, University of Copenhagen, Copenhagen, Denmark. Electronic address: jomo@sund.ku.dk.
Jazyk:	angličtina
Zdroj:	Gastroenterology [Gastroenterology] 2023 Jul; Vol. 165 (1), pp. 121-132.e5. Date of Electronic Publication: 2023 Mar 24.
DOI:	10.1053/j.gastro.2023.03.208
Abstrakt:	Background & Aims: Colonic adenomatous polyps, or adenomas, are frequent precancerous lesions and the origin of most cases of colorectal adenocarcinoma. However, we know from epidemiologic studies that although most colorectal cancers (CRCs) originate from adenomas, only a small fraction of adenomas (3%-5%) ever progress to cancer. At present, there are no molecular markers to guide follow-up surveillance programs. Methods: We profiled, by mass spectrometry-based proteomics combined with machine learning analysis, a selected cohort of formalin-fixed, paraffin-embedded high-grade (HG) adenomas with long clinical follow-up, collected as part of the Danish national screening program. We grouped subjects in the cohort according to their subsequent history of findings: a nonmetachronous advanced neoplasia group (G0), with no new HG adenomas or CRCs up to 10 years after polypectomy, and a metachronous advanced neoplasia group (G1) where individuals developed a new HG adenoma or CRC within 5 years of diagnosis. Results: We generated a proteome dataset from 98 selected HG adenoma samples, including 20 technical replicates, of which 45 samples belonged to the nonmetachronous advanced neoplasia group and 53 to the metachronous advanced neoplasia group. The clear distinction of these 2 groups seen in a uniform manifold approximation and projection plot indicated that the information contained within the abundance of the ∼5000 proteins was sufficient to predict the future occurrence of HG adenomas or development of CRC. Conclusions: We performed an in-depth analysis of quantitative proteomic data from 98 resected adenoma samples using various novel algorithms and statistical packages and found that their proteome can predict development of metachronous advanced lesions and progression several years in advance. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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