Affiliations: Dublin-Oxford Glycobiology Laboratory, NIBRT, Conway
Institute, UCD, Dublin, Ireland | Oxford Glycobiology Institute, Department of
Biochemistry, University of Oxford, Oxford, UK
Abstract: Ovarian cancer is the most lethal of all gynaecological cancers
among women. Serum CA125 is the only biomarker that is used routinely and there
is a need for further complementary biomarkers both in terms of sensitivity and
specificity. N-glycosylation changes in ovarian cancer serum
glycoproteins include a decrease in galactosylation of IgG and an increase in
sialyl Lewis X (SLe^{x}) on haptoglobin β-chain,
α1-acid glycoprotein and
α1-antichymotrypsin. These changes are also present in
chronic inflammation but not in malignant melanoma, where there are low levels
of inflammatory processes. Acute phase proteins carrying increased amounts of
SLe^{x} have an increased half-life. Sialylation of
acute phase proteins also decreases apoptosis favouring survival of cancer
cells. Cancer cells produce inflammatory cytokines which influence
glycosylation processing in liver parenchymal cells. Altered glycosylation of
the acute phase protein transferrin plays an important role in iron
homeostasis. Glycosylated transferrin and its glycans have anti-apoptotic
properties and many transferrin receptors in carcinoma could play a role in
development of anaemia. Decreased galactosylation and sialylation of IgG
increases the cytotoxicity of natural killer cells and complement activation
via mannose-binding lectin (MBL). Altered glycosylation of acute phase proteins
and IgG suggests that cancer regulates certain pathways favouring cancer cells
survival.
