Comparative glycomic profiling in esophageal adenocarcinoma.
OBJECTIVE
Aberrant glycosylation has been implicated in various types of cancers. Cancerous cells with altered glycosylation of their surface proteins shed such proteins into the circulating fluids. Glycomic profiling of such fluids shows the altered glycosylation. We performed glycomic profiling of serum from patients with no known disease, Barrett's without dysplasia, with high-grade dysplasia, and with esophageal adenocarcinoma in an attempt to delineate distinct differences in glycosylation among these groups.


METHODS
Serum samples from patients with Barrett's metaplasia (N = 5), high-grade dysplasia (N = 11), and esophageal adenocarcinoma (N = 50) were collected; samples from 18 healthy volunteers were used as control. Serum N-glycans were enzymatically released and then applied to both C18 Sep-Pak (Waters, Milford, MA) cartridges and activated charcoal cartridges. N-glycans were permethylated and then spotted directly onto a matrix-assisted laser desorption ionization plate. Mass spectra were acquired using the Applied Biosystems 4800 MALDI TOF/TOF Analyzer (Applied Biosystems Inc, Framingham, Mass). The obtained matrix-assisted laser desorption ionization-mass spectrometry data were processed using DataExplorer files (Applied Biosystems Inc) listing m/z values and intensities.


RESULTS
The intensities of 98 glycans were significantly different among the 3 groups; 26 of these corresponded to known glycan structures. Pairwise comparisons showed that 8 glycans were significantly different in all 3 pairwise comparisons.


CONCLUSIONS
We demonstrated that comparative glycomic profiling of esophageal adenocarcinoma reveals a subset of glycans that can be selected as candidate biomarkers. These markers can differentiate normal from high-grade dysplasia, normal from esophageal adenocarcinoma, and high-grade dysplasia from esophageal adenocarcinoma. Further validation will be necessary to determine the clinical utility of these glycan biomarkers.
Hammoud
Zane T
ZT
Cardiothoracic Surgery, Henry Ford Health System, Detroit, Mich. 48202, USA. Zhammou1@hfhs.org
Mechref
Yehia
Y
Hussein
Ahmed
A
Bekesova
Slavka
S
Zhang
Min
M
Kesler
Kenneth A
KA
Novotny
Milos V
MV
D000230:Adenocarcinoma / Q000097:blood* / Q000473:pathology; D001471:Barrett Esophagus / Q000097:blood* / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D004938:Esophageal Neoplasms / Q000097:blood* / Q000473:pathology; D054794:Glycomics / Q000379:methods; D006031:Glycosylation; D006801:Humans; D008679:Metaplasia; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000097:blood*; D011230:Precancerous Conditions / Q000097:blood* / Q000473:pathology; D025341:Principal Component Analysis; D011499:Protein Processing, Post-Translational; D015203:Reproducibility of Results; D052616:Solid Phase Extraction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D015415:Biomarkers; D011134:Polysaccharides