Ovarian cancer is associated with changes in glycosylation in both acute-phase proteins and IgG.
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 (SLe(x)). 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, alpha1-acid glycoprotein, and alpha1-antichymotrypsin from patients contained elevated levels of subsets of glycoforms containing SLe(x). 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.
Saldova
Radka
R
Department of Biochemistry, Oxford Glycobiology Institute, University of Oxford, Oxford, UK.
Royle
Louise
L
Radcliffe
Catherine M
CM
Abd Hamid
Umi M
UM
Evans
Rachel
R
Arnold
James N
JN
Banks
Rosamonde E
RE
Hutson
Richard
R
Harvey
David J
DJ
Antrobus
Robin
R
Petrescu
Stefana M
SM
Dwek
Raymond A
RA
Rudd
Pauline M
PM
D000209:Acute-Phase Proteins / Q000737:chemistry*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000737:chemistry; D002236:Carbohydrate Conformation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D054794:Glycomics; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000737:chemistry*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000097:blood / Q000378:metabolism* / Q000473:pathology*; D011134:Polysaccharides / Q000737:chemistry; D012680:Sensitivity and Specificity; D000514:alpha 1-Antichymotrypsin / Q000737:chemistry
D000209:Acute-Phase Proteins; D015415:Biomarkers; D007074:Immunoglobulin G; D011134:Polysaccharides; D000514:alpha 1-Antichymotrypsin