Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients

Previous
studies indicated that glycans in serum may serve as biomarkers
for diagnosis of ovarian cancer; however, it was unclear to which
proteins these glycans belong. We hypothesize that protein-specific
glycosylation profiles of the glycans may be more informative of ovarian
cancer and can provide insight into biological mechanisms underlying
glycan aberration in serum of diseased individuals. Serum samples
from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin
(IgG, IgA, and IgM) concentrations and glycosylation profiles were
quantified using multiple reaction monitoring mass spectrometry. Differential
and classification analyses were performed to identify aberrant protein-specific
glycopeptides using a training set. All findings were validated in
an independent test set. Multiple glycopeptides from immunoglubins
IgA, IgG, and IgM were found to be differentially expressed in serum
of EOC patients compared with controls. The protein-specific glycosylation
profiles showed their potential in the diagnosis of EOC. In particular,
IgG-specific glycosylation profiles are the most powerful in discriminating
between EOC case and controls. Additional studies of protein- and
site-specific glycosylation profiles of immunoglobulins and other
proteins will allow further elaboration on the characteristics of
biological functionality and causality of the differential glycosylation
in ovarian cancer and thus ultimately lead to increased sensitivity
and specificity of diagnosis.