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Ultra performance liquid chromatographic profiling of serum N-glycans for fast and efficient identification of cancer associated alterations in glycosylation

Authors :
Bones, Jonathan
Mittermayr, Stefan
ODonoghue, Niaobh
Guttman, Andras
Rudd, Pauline M.
Source :
Analytical Chemistry. Dec 15, 2010, Vol. 82 Issue 24, p10208, 8 p.
Publication Year :
2010

Abstract

Glycosylation is a diverse but critically important posttranslational modification that modulates the physical, chemical and biological properties of proteins. Alterations in glycosylation have been noted in a number of diseases including cancer. The discovery of alterations in the glycosylation of serum glycoproteins which may offer potential as biomarkers is attracting considerable research interest. In the current study, the significant improvements in efficiency, selectivity, and analysis speed offered by ultra performance liquid chromatography (UPLC) profiling of fluorescently labeled N-linked oligosaccharides on a recently introduced sub-2 [micro]m hydrophilic interaction (HILIC) based stationary phase are demonstrated to identify cancer associated alterations in the serum N-glycome of patients bearing stomach adenocarcinoma. The contribution of the glycosylation present on four highly abundant serum proteins namely, IgG, hapteglobin, transferrin, and [alpha]1-acid glycoprotein was evaluated. Alterations in the glycosylation present on these four proteins isolated from the pathologically staged cancer serum using either affinity purification or two-dimensional electrophoresis were then investigated as possible markers for stomach cancer progression. In agreement with previous reports, an increase in sialylation was observed on haptoglobin, transferrin, and [alpha]1-acid glycoprotein in the cancerous state. Increased levels of core fucosylated biantennary glycans and decreased levels of monogalactosylated core fucosylated biantennary glycans were present on IgG with increasing disease pro. gression. The speed and selectivity offered by the sub-2 [micro]m HILIC phase make it ideal for rapid yet highly efficient separation of complex oligosaccharide mixtures such as that present in the serum N-glycome. 10.1021/ac102860w

Details

Language :
English
ISSN :
00032700
Volume :
82
Issue :
24
Database :
Gale General OneFile
Journal :
Analytical Chemistry
Publication Type :
Academic Journal
Accession number :
edsgcl.245540858