Glycobiology Advance Access originally published online on September 25, 2008
Glycobiology 2008 18(12):1105-1118; doi:10.1093/glycob/cwn095
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A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression
6 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford, OX1 3QU
7 Tumor Immunology Group, University of Nottingham, Division of Breast Surgery, Nottingham City Hospital, Hucknall Road, Nottingham, NG5 1PB, UK
1 To whom correspondence should be addressed: Tel: +353-1716-6728; Fax: +353-1716-6728; e-mail: pauline.rudd{at}nibrt.ie
Received on June 20, 2008; revised on September 5, 2008; accepted on September 22, 2008
Aberrant glycosylation on glycoproteins that are either presented on the surface or secreted by cancer cells is a potential source of disease biomarkers and provides insights into disease pathogenesis. N-Glycans of the total serum glycoproteins from advanced breast cancer patients and healthy individuals were sequenced by HPLC with fluorescence detection coupled with exoglycosidase digestions and mass spectrometry. We observed a significant increase in a trisialylated triantennary glycan containing 
1,3-linked fucose which forms part of the sialyl Lewis x epitope. Following digestion of the total glycan pool with a combination of sialidase and β-galactosidase, we segregated and quantified a digestion product, a monogalactosylated triantennary structure containing 1,3-linked fucose. We compared breast cancer patients and controls and detected a 2-fold increase in this glycan marker in patients. In 10 patients monitored longitudinally, we showed a positive correlation between this glycan marker and disease progression and also demonstrated its potential as a better indicator of metastasis compared to the currently used biomarkers, CA 15-3 and carcinoembryonic antigen (CEA). A pilot glycoproteomic study of advanced breast cancer serum highlighted acute-phase proteins 1-acid glycoprotein, 1-antichymotrypsin, and haptoglobin β-chain as contributors to the increase in the glycan marker which, when quantified from each of these proteins, marked the onset of metastasis in advance of the CA 15-3 marker. These preliminary findings suggest that specific glycans and glycoforms of proteins may be candidates for improved markers in the monitoring of breast cancer progression.
Key words: breast cancer / N-linked glycans / acute-phase proteins / sLex / biomarker
2 Present address: Dublin-Oxford NIBRT Glycobiology Laboratory, NIBRT, Conway Institute, University College Dublin, Belfield, Dublin 4, Ireland.
3 Present address: Ludger, Culham Science Centre, Abingdon, Oxfordshire, OX14 3EB, UK.
4 Present address: Lonza Biologics plc, 228 Bath Road, Slough, SL1 4DX, UK.
5 Present address: Laboratorio de Endocrinología Molecular, Facultad de Medicina, Universidade de Santiago de Compostela, Rua San Francisco s/n, 15782 Santiago de Compostela, Spain.