Quantitative Serum Glycomics of Esophageal Adenocarcinoma and Other Esophageal Disease Onsets

Abstract

Aberrant glycosylation has been implicated in various types of cancers and changes in glycosylation may be associated with signaling pathways during malignant transformation. Glycomic profiling of blood serum, in which cancer cell proteins or their fragments with altered glycosylation patterns are shed, could reveal the altered glycosylation. We performed glycomic profiling of serum from patients with no known disease (N=18), patients with high grade dysplasia (HGD, N=11) and Barrett’s (N=5), and patients with esophageal adenocarcinoma (EAC, N=50) in an attempt to delineate distinct differences in glycosylation between these groups. The relative intensities of 98 features were significantly different among the disease onsets; 26 of these correspond to known glycan structures. The changes in the relative intensities of three of the known glycan structures predicted esophageal adenocarcinoma with 94% sensitivity and better than 60% specificity as determined by receiver operating characteristic (ROC) analysis. We have demonstrated that comparative glycomic profiling of EAC reveals a subset of glycans that can be selected as candidate biomarkers. These markers can differentiate disease-free from HGD, disease-free from EAC, and HGD from EAC. The clinical utility of these glycan biomarkers requires further validation.

Current advances in esophageal cancer proteomics

“…Mechref et al performed glycosylation profiling of serum samples from patients with EAC, high-grade dysplasia, Barrett's esophagus, and healthy individuals and showed that the changes in the relative intensities of three glycan structures predicted EAC with 94% sensitivity and more than 60% specificity [39], suggesting that comparative EAC glycomics can be used for the identification of EAC candidate biomarkers.…”

Early Diagnostic Biomarkers for Esophageal Adenocarcinoma—The Current State of Play

“…They identified 98 glycan features with different intensities in disease onsets and 26 of them correspond to known glycan structures. They showed statistically significant glycan changes between 4 different conditions (Healthy/BE/HGD/EAC) with 3 of the known potential N-glycan biomarkers predicting EAC with 94% sensitivity and 60% specificity (135). Another study used microchip electrophoresis with laser-induced fluorescence detection for N-glycan profiling and were able to differentiate between the healthy, Barrett's esophagus, HGD, and EAC conditions (136).…”

Human Sperm Binding Is Mediated by the Sialyl-Lewis x Oligosaccharide on the Zona Pellucida

“…1, shaded grey), that differs from the other families in having no core fucosylation. The human plasma glycome is characterized by the absence of core fucose plus high levels of 2-6 sialylation (13,14). Therefore we concluded that this fourth glycan family was largely derived from the follicular fluid constituents that co-purify with ZP (Table S1).…”