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

Fanny Boyaval, Hans Dalebout, René van Zeijl, Wenjun Wang, Arantza Fariña-Sarasqueta, Guinevere S. M. Lageveen-Kammeijer, Jurjen J. Boonstra, Liam A. McDonnell, Manfred Wuhrer, Hans Morreau, Bram Heijs

Research output: Contribution to journalArticleAcademicpeer-review

23 Citations (Scopus)

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.
Original languageEnglish
Article number1552
JournalCancers
Volume14
Issue number6
DOIs
Publication statusPublished - 1 Mar 2022

Keywords

  • Colorectal cancer
  • Early cancer progression
  • MALDI-MSI
  • Mass spectrometry imaging
  • Molecular histology
  • N-glycosylation

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