Association of N‑Glycosylation with Breast Carcinoma and Systemic Features Using High-Resolution Quantitative UPLC

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....

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Bibliographic Details
Published in:Journal of proteome research 2014-05, Vol.13 (5), p.2314-2327
Main Authors: Saldova, Radka, Asadi Shehni, Akram, Haakensen, Vilde D, Steinfeld, Israel, Hilliard, Mark, Kifer, Ilona, Helland, Åslaug, Yakhini, Zohar, Børresen-Dale, Anne-Lise, Rudd, Pauline M
Format: Article
Language:English
Subjects:
Adult
Aged
Aged, 80 and over
Breast Neoplasms - blood
Breast Neoplasms - diagnosis
Breast Neoplasms - metabolism
Chromatography, High Pressure Liquid - methods
Cluster Analysis
Female
Glycomics - methods
Glycosylation
Humans
Male
Middle Aged
Polysaccharides - blood
Polysaccharides - classification
Polysaccharides - metabolism
Reproducibility of Results
Sensitivity and Specificity
Young Adult
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Summary: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.
ISSN:1535-3893
1535-3907
DOI:10.1021/pr401092y