A strategy to reveal potential glycan markers from serum glycoproteins associated with breast cancer progression.
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.
Abd Hamid
Umi M
UM
Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, South Parks Road, Oxford OX13QU, UK.
Royle
Louise
L
Saldova
Radka
R
Radcliffe
Catherine M
CM
Harvey
David J
DJ
Storr
Sarah J
SJ
Pardo
Maria
M
Antrobus
Robin
R
Chapman
Caroline J
CJ
Zitzmann
Nicole
N
Robertson
John F
JF
Dwek
Raymond A
RA
Rudd
Pauline M
PM
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
D014408:Biomarkers, Tumor; D006023:Glycoproteins; D011134:Polysaccharides