Glycosite mapping and in situ mass spectrometry imaging of MUC2 glycopeptides via on-slide mucinase digestion.
basic_science · Level V
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- Record sourced from PubMed, PMID 42098121.
- Also identified by DOI 10.1038/s41467-026-72853-3.
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Abstract
Current analytical techniques are limited in their ability to interrogate the mechanistic relationship between aberrant mucin glycosylation and malignancy. Herein, we describe a method for mapping specific mucin glycoforms in diseased tissue, enabling correlation of the tumor glycan profile with malignant features. Following on-tissue digestion with mucinase StcE, matrix-assisted laser desorption ionization mass spectrometry imaging (MALDI-MSI) deduces the spatial distribution of mucinous O-glycopeptides that are subsequently identified using liquid chromatography coupled to mass spectrometry (LC-MS). Our coupled MS approach reveals a striking mucin 2 (MUC2) expression pattern in three colorectal mucinous adenocarcinomas, in which different glycoforms clearly stratify regions within each tumor. The LC-MS experiments obtain glycoproteomic sequence coverage of MUC2's mucin domains in unprecedented depth, and we also present evidence for an endogenous O-acetylated GalNAc. Overall, this proof-of-concept work underscores the potential of this technique to drive research in oncology and beyond.