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

Cancers

René Van Zeijl¹  Bram Heijs¹  Manfred Wuhrer¹  Hans Dalebout¹  Guinevere S. M. Lageveen-Kammeijer¹  Wenjun Wang¹  Jurjen J. Boonstra²  Arantza Fariña-Sarasqueta³  Hans Morreau⁴  Fanny Boyaval⁴  Liam A. McDonnell⁵ 

[1] Center for Proteomics & Metabolomics, Leiden University Medical Center, Albinusdreef, 2333 ZA Leiden, The Netherlands;Department of Gastroenterology and Hepatology, Leiden University Medical Centre, 2300 RC Leiden, The Netherlands;Department of Pathology, Cancer Center Amsterdam, Amsterdam University Medical Centers, University of Amsterdam, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Department of Pathology, Leiden University Medical Center, Albinusdreef, 2333 ZA Leiden, The Netherlands;Fondazione Pisana per la Scienza ONLUS, Via Ferruccio Giovannini, 56017 San Giuliano Terme, Italy;

关键词: colorectal cancer;    N-glycosylation;    mass spectrometry imaging;    MALDI-MSI;    molecular histology;    early cancer progression;   

DOI  :  10.3390/cancers14061552

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown