N-linked Glycan Structures and Their Expressions Change in the Blood Sera of Ovarian Cancer Patients

Glycosylated proteins play important roles in a broad
spectrum
of biochemical and biological processes, and prior reports have suggested
that changes in protein glycosylation occur during cancer initiation
and progression. Ovarian cancer (OC) is a fatal malignancy, most commonly
diagnosed after the development of metastases. Therefore, early detection
of OC is key to improving survival. To this end, specific changes
of the serum glycome have been proposed as possible biomarkers for
different types of cancers. In this study, we extend this concept
to OC. To characterize differences in total N-glycan levels, serum
samples provided by 20 healthy control women were compared to those
acquired from patients diagnosed with late-stage recurrent OC who
were enrolled in an experimental treatment trial prior to receiving
therapy (N = 19) and one month later, prior to the
second treatment cycle (N = 11). Additionally, analyses
of the N-glycans associated with IgG and characterization of the relative
abundance levels of core vs outer-arm fucosylation were also performed.
The N-linked glycomic profiles revealed increased abundances of tri-
and tetra-branched structures with varying degrees of sialylation
and fucosylation and an apparent decrease in the levels of “bisecting”
glycans in OC samples compared to controls. Increased levels of a-galactosylation
structures were observed on N-linked glycans derived from IgG, which
were independent of the presence of fucose residues. Elevated levels
of outer-arm fucosylation were also identified in the OC samples.
These results allowed the control samples to be distinguished from
the baseline ovarian cancer patients prior to receiving the experimental
treatment. In some cases, the pre-treatment samples could be distinguished
from the post-experimental treatment samples, as many of those patients
showed a further progression of the disease.