Glycobiology Advance Access published online on September 20, 2007
Glycobiology, doi:10.1093/glycob/cwm100
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Ovarian Cancer is Associated With Changes in Glycosylation in Both Acute-Phase Proteins and IgG
1 Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford, OX1 3QU, UK
2 Cancer Research UK Clinical Centre, St James's University Hospital, Leeds, LS9 7TF, UK
3 Dept of Obstetrics & Gynaecology, St James's University Hospital, Leeds, LS9 7TF, UK
4 Institute of Biochemistry, Bucharest 17, 060031, Romania
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 analyse simultaneously the glycosylation of protein glycoforms contained in single spots excised from a 2D gel (<1ng 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 tumours, 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
1 Current and correspondence address: Dublin-Oxford Glycobiology laboratory, NIBRT, Conway Institute, UCD, Dublin 4, Ireland, Phone: +353 1716 6728, Fax: +35317166950, Email address: pauline.rudd{at}nibrt.ie
2 Current address: National Heart and Lung Institute, Imperial College London, SW3 6LR, UK
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