title: A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression.
abstract: 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 alpha1,3-linked fucose which forms part of the sialyl Lewis x epitope. Following digestion of the total glycan pool with a combination of sialidase and beta-galactosidase, we segregated and quantified a digestion product, a monogalactosylated triantennary structure containing alpha1,3-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 alpha1-acid glycoprotein, alpha1-antichymotrypsin, and haptoglobin beta-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.
authors.affiliation: Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX13QU, UK.
authors.forename: Umi M
authors.initials: UM
authors.lastname: Abd Hamid
authors.forename: Louise
authors.initials: L
authors.lastname: Royle
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Radcliffe
authors.forename: David J
authors.initials: DJ
authors.lastname: Harvey
authors.forename: Sarah J
authors.initials: SJ
authors.lastname: Storr
authors.forename: Maria
authors.initials: M
authors.lastname: Pardo
authors.forename: Robin
authors.initials: R
authors.lastname: Antrobus
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Chapman
authors.forename: Nicole
authors.initials: N
authors.lastname: Zitzmann
authors.forename: John F
authors.initials: JF
authors.lastname: Robertson
authors.forename: Raymond A
authors.initials: RA
authors.lastname: Dwek
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood* / Q000473:pathology*; D002851:Chromatography, High Pressure Liquid; D018450:Disease Progression; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D006801:Humans; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood*; D012189:Retrospective Studies
chemical_list: D014408:Biomarkers, Tumor; D006023:Glycoproteins; D011134:Polysaccharides