Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia
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Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia. / Bech, Jacob Mathias; Terkelsen, Thilde; Bartels, Annette Snejbjerg; Coscia, Fabian; Doll, Sophia; Zhao, Siqi; Zhang, Zhaojun; Brünner, Nils; Lindebjerg, Jan; Madsen, Gunvor Iben; Fang, Xiangdong; Mann, Matthias; Afonso Moreira, José Manuel.
I: Gastroenterology, Bind 165, Nr. 1, 2023, s. 121-132.e5.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Proteomic Profiling of Colorectal Adenomas Identifies a Predictive Risk Signature for Development of Metachronous Advanced Colorectal Neoplasia
AU - Bech, Jacob Mathias
AU - Terkelsen, Thilde
AU - Bartels, Annette Snejbjerg
AU - Coscia, Fabian
AU - Doll, Sophia
AU - Zhao, Siqi
AU - Zhang, Zhaojun
AU - Brünner, Nils
AU - Lindebjerg, Jan
AU - Madsen, Gunvor Iben
AU - Fang, Xiangdong
AU - Mann, Matthias
AU - Afonso Moreira, José Manuel
N1 - Funding Information: Funding This work was supported by a grant from the Sawmill Owner Jeppe Juhl and Wife Ovita Juhl Memorial Foundation. Jacob Mathias Bech was supported by a PhD scholarship from Sino-Danish Center. Fabian Coscia acknowledges the European Union’s Horizon 2020 Research and Innovation Programme under grant agreement 846795 (Marie Skłodowska-Curie grant) and support by the German Federal Ministry of Education and Research (BMBF), as part of the National Research Initiatives for Mass Spectrometry in Systems Medicine, under grant agreement 161L0222. Funding Information: Funding This work was supported by a grant from the Sawmill Owner Jeppe Juhl and Wife Ovita Juhl Memorial Foundation. Jacob Mathias Bech was supported by a PhD scholarship from Sino-Danish Center. Fabian Coscia acknowledges the European Union's Horizon 2020 Research and Innovation Programme under grant agreement 846795 (Marie Skłodowska-Curie grant) and support by the German Federal Ministry of Education and Research (BMBF), as part of the National Research Initiatives for Mass Spectrometry in Systems Medicine, under grant agreement 161L0222. Publisher Copyright: © 2023 The Authors
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - Biomarkers
KW - Colonic Adenomatous Polyps
KW - Colorectal Cancer
KW - Progression
U2 - 10.1053/j.gastro.2023.03.208
DO - 10.1053/j.gastro.2023.03.208
M3 - Journal article
C2 - 36966943
AN - SCOPUS:85160103472
VL - 165
SP - 121-132.e5
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 1
ER -
ID: 357511480