Glycosylation Changes of Serum Glycoproteins in Ovarian Cancer May Contribute to Disease Pathogenesis

Abstract

Ovarian cancer is the most lethal of all gynecological cancers. Although serum biomarker CA125 is routinely used, there is a need for sensitive and specific complementary biomarkers. 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 inflammations but not in malignant melanoma with low levels of inflammation. Acute phase proteins carrying increased amounts of SLe^x have an increased half-life. Sialylation of acute phase proteins decreases apoptosis favouring survival of cancer cells. Cancer cells produce inflammatory cytokines which influence glycosylation in liver parenchymal cells. The decreased galactosylation and sialylation of IgG increases cytotoxicity of natural killer cells and complement activation via mannose-binding lectin. Altered glycosylation of acute phase proteins and IgG suggests that cancer regulates certain pathways favouring survival of cancer cells.