Glycobiology Advance Access originally published online on September 20, 2007
Glycobiology 2007 17(12):1344-1356; doi:10.1093/glycob/cwm100
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Ovarian Cancer is Associated with Changes in Glycosylation in Both Acute-Phase Proteins and IgG
4 Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford OX1 3QU, UK;
5 Cancer Research UK Clinical Centre, and St James's University Hospital, Leeds LS9 7TF, UK;
6 Department of Obstetrics and Gynaecology, St James's University Hospital, Leeds LS9 7TF, UK;
7 Institute of Biochemistry, Splaiul Independentei 296, 060031 Bucharest 17, Romania
1 To whom correspondence should be addressed: Tel: +353-17166728; Fax: +353-17166950; e-mail: pauline.rudd{at}nibrt.ie
Received on May 28, 2007; revised on August 20, 2007; accepted on September 9, 2007
Ovarian cancer is the fourth most common cancer in women in the Western world. In a pilot scale study, we highlight changes in the total serum glycome of patients with advanced ovarian cancer that might shed insight into disease pathogenesis. These changes include increases in levels of core fucosylated, agalactosyl biantennary glycans (FA2) and sialyl Lewis x (SLex). To investigate further which proteins contribute to these alterations, we developed technology to analyze simultaneously the glycosylation of protein glycoforms contained in single spots excised from a 2D gel (<1 ng protein). The acute-phase proteins, haptoglobin,
1-acid glycoprotein, and
1-antichymotrypsin from patients contained elevated levels of subsets of glycoforms containing SLex. We also established that IgG heavy chains from patients contained twice the level of FA2 compared with healthy controls. Serum CA125 is the only biomarker that is used routinely, and there is a need for complementary markers that will improve both sensitivity and specificity. There was some preliminary indication that combinations of changes in the serum glycome might improve the separation of ovarian cancer and benign tumors; however, a larger study using data receiver operating characteristic curves will be required to draw any firm conclusions.
Key words: acute-phase proteins / biomarker / IgG / N-linked glycans / ovarian cancer
2 Present address: Dublin-Oxford Glycobiology Laboratory, NIBRT, Conway Institute, University College of Dublin, Belfield, Dublin 4, Ireland
3 Present address: National Heart and Lung Institute, Imperial College London SW3 6LR, UK
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