title: Association of N-glycosylation with breast carcinoma and systemic features using high-resolution quantitative UPLC.
abstract: An improved separation of the human serum N-glycome using hydrophilic interaction chromatography technology with UPLC is described, where more than 140 N-glycans were assigned. Using this technique, serum samples from 107 healthy controls and 62 newly diagnosed breast cancer patients were profiled. The most statistically significant alterations were observed in cancer patients compared with healthy controls: an increase in sialylation, branching, and outer-arm fucosylation and a decrease in high-mannosylated and biantennary core-fucosylated glycans. In the controls and cases combined systemic features were analyzed; serum estradiol was associated with increase in digalactosylated glycans, and higher mammographic density was associated with increase in biantennary digalactosylated glycans and with decrease in trisialylated and in outer-arm fucosylated glycans. Furthermore, particular glycans were altered in some features of the breast carcinomas; bisected biantennary nonfucosylated glycans were decreased in patients with progesterone receptor positive tumors, and core-fucosylated biantennary bisected monogalactosylated glycans were decreased in patients with the TP53 mutation. Systemic features show more significant associations with the serum N-glycome than do the features of the breast carcinomas. In conclusion, the UPLC-based glycan analysis technique described here reveals highly significant differences between healthy women and breast cancer patients. Significant associations with breast carcinoma and systemic features are described.
authors.affiliation: NIBRT GlycoScience Group, National Institute for Bioprocessing Research and Training , Fosters Avenue, Mount Merrion, Blackrock, Dublin 4, Ireland.
authors.forename: Radka
authors.initials: R
authors.lastname: Saldova
authors.forename: Akram
authors.initials: A
authors.lastname: Asadi Shehni
authors.forename: Vilde D
authors.initials: VD
authors.lastname: Haakensen
authors.forename: Israel
authors.initials: I
authors.lastname: Steinfeld
authors.forename: Mark
authors.initials: M
authors.lastname: Hilliard
authors.forename: Ilona
authors.initials: I
authors.lastname: Kifer
authors.forename: Aslaug
authors.initials: A
authors.lastname: Helland
authors.forename: Zohar
authors.initials: Z
authors.lastname: Yakhini
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: Pauline M
authors.initials: PM
authors.lastname: Rudd
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood / Q000175:diagnosis / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D016000:Cluster Analysis; D005260:Female; D054794:Glycomics / Q000379:methods*; D006031:Glycosylation; D006801:Humans; D008297:Male; D008875:Middle Aged; D011134:Polysaccharides / Q000097:blood / Q000145:classification / Q000378:metabolism*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D055815:Young Adult
chemical_list: D011134:Polysaccharides