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High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer

SIMPLE SUMMARY: The detection of colorectal cancer (CRC) at an early stage is increasing due to the implementation of screening programs. Local excision of early CRC is potentially curative, however the identification of early lesions at high risk of regional metastases remains challenging, and grea...

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Autores principales: Boyaval, Fanny, Dalebout, Hans, Van Zeijl, René, Wang, Wenjun, Fariña-Sarasqueta, Arantza, Lageveen-Kammeijer, Guinevere S. M., Boonstra, Jurjen J., McDonnell, Liam A., Wuhrer, Manfred, Morreau, Hans, Heijs, Bram
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945895/
https://www.ncbi.nlm.nih.gov/pubmed/35326703
http://dx.doi.org/10.3390/cancers14061552
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author Boyaval, Fanny
Dalebout, Hans
Van Zeijl, René
Wang, Wenjun
Fariña-Sarasqueta, Arantza
Lageveen-Kammeijer, Guinevere S. M.
Boonstra, Jurjen J.
McDonnell, Liam A.
Wuhrer, Manfred
Morreau, Hans
Heijs, Bram
author_facet Boyaval, Fanny
Dalebout, Hans
Van Zeijl, René
Wang, Wenjun
Fariña-Sarasqueta, Arantza
Lageveen-Kammeijer, Guinevere S. M.
Boonstra, Jurjen J.
McDonnell, Liam A.
Wuhrer, Manfred
Morreau, Hans
Heijs, Bram
author_sort Boyaval, Fanny
collection PubMed
description SIMPLE SUMMARY: The detection of colorectal cancer (CRC) at an early stage is increasing due to the implementation of screening programs. Local excision of early CRC is potentially curative, however the identification of early lesions at high risk of regional metastases remains challenging, and greatly influencing therapy decision making. Variations in sugar molecules has been associated with development and progression in various cancer types including CRC. Therefore, we examined these sugar signatures, so-called N-glycans, in different stages of progression of CRC starting from epithelium to pre-cancerous and cancerous tissue. We report that the sugar signatures clearly differentiate each step of CRC progression, especially between pre-cancerous and cancerous tissue. We also observed some of the glycosylation signatures of the cancerous areas to be spreading into the tumor microenvironment. ABSTRACT: The increase incidence of early colorectal cancer (T1 CRC) last years is mainly due to the introduction of population-based screening for CRC. T1 CRC staging based on histological criteria remains challenging and there is high variability among pathologists in the scoring of these criteria. It is crucial to unravel the biology behind the progression of adenoma into T1 CRC. Glycomic studies have reported extensively on alterations of the N-glycomic pattern in CRC; therefore, investigating these alterations may reveal new insights into the development of T1 CRC. We used matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) to spatially profile the N-glycan species in a cohort of pT1 CRC using archival formalin-fixed and paraffin-embedded (FFPE) material. To generate structural information on the observed N-glycans, CE-ESI-MS/MS was used in conjunction with MALDI-MSI. Relative intensities and glycosylation traits were calculated based on a panel of 58 N-glycans. Our analysis showed pronounced differences between normal epithelium, dysplastic, and carcinoma regions. High-mannose-type N-glycans were higher in the dysplastic region than in carcinoma, which correlates to increased proliferation of the cells. We observed changes in the cancer invasive front, including higher expression of α2,3-linked sialic acids which followed the glycosylation pattern of the carcinoma region.
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spelling pubmed-89458952022-03-25 High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer Boyaval, Fanny Dalebout, Hans Van Zeijl, René Wang, Wenjun Fariña-Sarasqueta, Arantza Lageveen-Kammeijer, Guinevere S. M. Boonstra, Jurjen J. McDonnell, Liam A. Wuhrer, Manfred Morreau, Hans Heijs, Bram Cancers (Basel) Article SIMPLE SUMMARY: The detection of colorectal cancer (CRC) at an early stage is increasing due to the implementation of screening programs. Local excision of early CRC is potentially curative, however the identification of early lesions at high risk of regional metastases remains challenging, and greatly influencing therapy decision making. Variations in sugar molecules has been associated with development and progression in various cancer types including CRC. Therefore, we examined these sugar signatures, so-called N-glycans, in different stages of progression of CRC starting from epithelium to pre-cancerous and cancerous tissue. We report that the sugar signatures clearly differentiate each step of CRC progression, especially between pre-cancerous and cancerous tissue. We also observed some of the glycosylation signatures of the cancerous areas to be spreading into the tumor microenvironment. ABSTRACT: The increase incidence of early colorectal cancer (T1 CRC) last years is mainly due to the introduction of population-based screening for CRC. T1 CRC staging based on histological criteria remains challenging and there is high variability among pathologists in the scoring of these criteria. It is crucial to unravel the biology behind the progression of adenoma into T1 CRC. Glycomic studies have reported extensively on alterations of the N-glycomic pattern in CRC; therefore, investigating these alterations may reveal new insights into the development of T1 CRC. We used matrix-assisted laser desorption ionization (MALDI) mass spectrometry imaging (MSI) to spatially profile the N-glycan species in a cohort of pT1 CRC using archival formalin-fixed and paraffin-embedded (FFPE) material. To generate structural information on the observed N-glycans, CE-ESI-MS/MS was used in conjunction with MALDI-MSI. Relative intensities and glycosylation traits were calculated based on a panel of 58 N-glycans. Our analysis showed pronounced differences between normal epithelium, dysplastic, and carcinoma regions. High-mannose-type N-glycans were higher in the dysplastic region than in carcinoma, which correlates to increased proliferation of the cells. We observed changes in the cancer invasive front, including higher expression of α2,3-linked sialic acids which followed the glycosylation pattern of the carcinoma region. MDPI 2022-03-18 /pmc/articles/PMC8945895/ /pubmed/35326703 http://dx.doi.org/10.3390/cancers14061552 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Boyaval, Fanny
Dalebout, Hans
Van Zeijl, René
Wang, Wenjun
Fariña-Sarasqueta, Arantza
Lageveen-Kammeijer, Guinevere S. M.
Boonstra, Jurjen J.
McDonnell, Liam A.
Wuhrer, Manfred
Morreau, Hans
Heijs, Bram
High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title_full High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title_fullStr High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title_full_unstemmed High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title_short High-Mannose N-Glycans as Malignant Progression Markers in Early-Stage Colorectal Cancer
title_sort high-mannose n-glycans as malignant progression markers in early-stage colorectal cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8945895/
https://www.ncbi.nlm.nih.gov/pubmed/35326703
http://dx.doi.org/10.3390/cancers14061552
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