Journal
ANALYTICAL CHEMISTRY
Volume 88, Issue 11, Pages 5904-5913Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.analchem.6b00819
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Funding
- ZonMW Zenith Project Imaging Mass Spectrometry-Based Molecular Histology: Differentiation and Characterization of Clinically Challenging Soft Tissue Sarcomas Grant [93512002]
- European Union Seventh Framework Programmes HighGlycan Project [278535]
- IBD-BIOM [305479]
- National Institutes of Health/National Cancer Institute [R21CA186799]
- state of South Carolina SmartState Endowed Research Program
- National Cancer Institute (NCI) [R01 CA120206, U01 CA168856]
- Hepatitis B Foundation
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Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging is a rapidly evolving field in which mass spectrometry techniques are applied directly on tissues to characterize the spatial distribution of various molecules such as lipids, protein/peptides, and recently also N-glycans. Glycans are involved in many biological processes and several glycan changes have been associated with different kinds of cancer, making them an interesting target group to study. An important analytical challenge for the study of glycans by MALDI mass spectrometry is the labile character of sialic acid groups which are prone to in-source/postsource decay, thereby biasing the recorded glycan profile. We therefore developed a linkage-specific sialic acid derivatization by dimethylamidation and subsequent amidation and transferred this onto formalin-fixed paraffin-embedded (FFPE) tissues for MALDI imaging of N-glycans. Our results show (i) the successful stabilization of sialic acids in a linkage specific manner, thereby not only increasing the detection range, but also adding biological meaning, (ii) that no noticeable lateral diffusion is induced during to sample preparation, (iii) the potential of mass spectrometry imaging to spatially characterize the N-glycan expression within heterogeneous tissues.
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