Analysis of the Human Cancer Glycome Identifies a Novel Group of Tumor-Associated N-Acetylglucosamine Glycan Antigens

¹Glykos Finland Ltd.; Departments of ²Surgery and ³Pathology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland; ⁴Department of Medical Biochemistry and Cell Biology, Göteborg University, Göteborg, Sweden; and ⁵Department of Pathology, University of Turku and Turku University Hospital, Turku, Finland

^* To whom correspondence should be addressed. E-mail: tero.satomaa{at}glykos.fi.

	Abstract

The cell surface is covered by a dense layer of protein- and lipid-linked glycans. Although it has been known that distinct glycan structures are associated with cancer, the whole spectrum of cancer-associated glycans has remained undiscovered. In the present study, we analyzed the protein-linked cancer glycome by matrix-assisted laser desorption/ionization time-of-flight mass spectrometric glycan profiling of cancer patient tissue samples. In lung cancer, we detected accumulation of a novel group of tumor-associated glycans. These protein-linked glycans carried abnormal nonreducing terminal -N-acetyl-D-glucosamine (GlcNAc) residues. A similar phenomenon was also detected in structural analyses of tumor-derived glycosphingolipids. This showed that glycan biosynthesis may dramatically change in cancer and that direct glycome analysis can detect the resulting marker glycans. Based on the structural knowledge, we further devised a covalent labeling technique for the detection of GlcNAc-expressing tumors with a specific transferase enzyme. In normal tissues, terminal GlcNAc antigens are capped by galactosylation. Similarly to common cancer-associated glycan antigens T, Tn, and sialyl-Tn, the newly discovered GlcNAc antigens result from incomplete glycosylation. In conclusion, the identified terminal GlcNAc glycans should be recognized as a novel class of tumor markers. [Cancer Res 2009;69(14):5811–9]

Key Words: cancer biomarkers, glycomics, mass spectrometry, glycosylation, N-acetylglucosamine