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Published on: February 7, 2025
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N-Glycomic Profiling of Microsatellite Unstable Colorectal Cancer
Iiris Ukkola1,2, Pirjo Nummela1,2, Annamari Heiskanen3
1HUSLAB, Department of Pathology, HUS Diagnostic Center, Helsinki University Hospital and University of Helsinki, 00029 Helsinki, Finland.
Cancers
|July 29, 2023
Summary
Microsatellite instability (MSI) colorectal cancers (CRCs) show distinct N-glycan profiles compared to microsatellite stable (MSS) tumors. These differences, particularly in acidic N-glycans, vary with tumor stage and BRAF mutation status, impacting CRC progression.
Area of Science:
- Biochemistry
- Oncology
- Glycomics
Background:
- Aberrant glycosylation is implicated in cancer progression and immune evasion.
- Colorectal cancers (CRCs) with microsatellite instability (MSI) exhibit distinct clinical behaviors compared to microsatellite stable (MSS) tumors.
- Understanding molecular differences in MSI CRC is crucial for targeted therapies.
Purpose of the Study:
- To compare N-glycan profiles of different colorectal cancer (CRC) molecular subgroups.
- To investigate the influence of tumor stage and BRAF mutation status on N-glycan profiles in MSI CRC.
- To identify characteristic glycan signatures associated with MSI CRC progression.
Main Methods:
- Mass spectrometry was employed to analyze N-glycan profiles.
- N-glycans from stage II and IV MSI CRC tumors (BRAF wild-type and mutated subgroups) were compared with paired non-neoplastic tissues.
- Stage II MSI CRC N-glycans were also compared with corresponding MSS CRC samples.
Main Results:
- Significant differences in N-glycan profiles were observed between MSI CRCs and control tissues, and between MSI and MSS CRCs.
- MSI CRC tumors displayed a lower relative abundance of high-mannose N-glycans compared to controls and MSS CRCs.
- Acidic N-glycans showed stage and BRAF mutation-dependent variations, with opposite trends in stages II and IV between BRAF mutated and wild-type MSI CRC subgroups.
Conclusions:
- Molecular subgroups of colorectal cancer possess distinct glycan profiles.
- These characteristic glycan profiles may contribute to the unique carcinogenic properties of MSI tumors.
- N-glycan profiling could offer insights into CRC subtypes and therapeutic strategies.

