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 esophagus (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.