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

Abstract

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-galactosylated 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.

Evaluation of Riproximin Binding Properties Reveals a Novel Mechanism for Cellular Targeting

“…N-Glycans are significantly altered in cancer too (10). The presence of immature (11) or highly branched core-fucosylated structures (12)(13)(14)(15) has been related to various types of tumors.…”

New Trends in the Study of Protein Glycosylation in Oncological Diseases

“…Zatímco zánět, rakovina a imunologické procesy jsou propojeny v soubor komplexních mokutinách. Současný výzkum ukázal ně kte ré rozdíly na úrovni glykoproteinů -tvorbě glykanů v různých typech nádorů [11][12][13][14][15]. Nicméně není stále jasné, které proteiny nesou tyto modifi kace, protože ve výše uvedených studiích byly měřeny glykany, jež byly enzymaticky nebo chemicky odštěpeny z bio logických vzorků.…”

“…Podle těchto hybridních struktur glykanů lze rozdělit pacientky do defi novaných skupin. Převzato z [13].…”

“…To ilustruje obr. 3 v rámci srovnání skupin 19 pacientek s rakovinou vaječníků, 11 pacientek se stejným onemocněním po chemoterapii [13] a 20 kontrolními jedinci. Srovnání na obr.…”

Glycoscience aids in biomarker discovery

“…Compositional mass profiling utilizes high-resolution mass spectrometry (MS) to rapidly separate and identify glycans based on accurate mass. Glycans may be chromatographically fractionated offline and spotted for MALDI (in applications where speed is desirable) (15,(26)(27)(28)(29)(30)(31)(32)(33); or, they may be separated online by methods such as reversed phase (RP) liquid chromatography (LC) immediately prior to introduction into the mass spectrometer via electrospray ionization (where greater sensitivity is necessary) (34)(35)(36). Compositional mass profiling describes the glycans present in a sample in relation to the number of hexoses (such as glucose, galactose, or mannose), N-acetylhexosamines, deoxyhexoses (typically fucose), and sialic acids (such as N-acetylneuraminic acid or N-glycolylneuraminic acid) that each glycan is composed of.…”