Focused glycomic analysis of the N-linked glycan biosynthetic pathway in ovarian cancer.
Epithelial ovarian cancer is the deadliest female reproductive tract malignancy in Western countries. Less than 25% of cases are diagnosed when the cancer is confined, however, pointing to the critical need for early diagnostics for ovarian cancer. Identifying the changes that occur in the glycome of ovarian cancer cells may provide an avenue to develop a new generation of potential biomarkers for early detection of this disease. We performed a glycotranscriptomic analysis of endometrioid ovarian carcinoma using human tissue, as well as a newly developed mouse model that mimics this disease. Our results show that the N-linked glycans expressed in both nondiseased mouse and human ovarian tissues are similar; moreover, malignant changes in the expression of N-linked glycans in both mouse and human endometrioid ovarian carcinoma are qualitatively similar. Lectin reactivity was used as a means for rapid validation of glycan structural changes in the carcinomas that were predicted by the glycotranscriptome analysis. Among several changes in glycan expression noted, the increase of bisected N-linked glycans and the transcripts of the enzyme responsible for its biosynthesis, GnT-III, was the most significant. This study provides evidence that glycotranscriptome analysis can be an important tool in identifying potential cancer biomarkers.
Abbott
Karen L
KL
Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA. kabbott@uga.edu
Nairn
Alison V
AV
Hall
Erica M
EM
Horton
Marc B
MB
McDonald
John F
JF
Moremen
Kelley W
KW
Dinulescu
Daniela M
DM
Pierce
Michael
M
D000217:Acyltransferases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D053898:Biosynthetic Pathways; D002240:Carbohydrate Sequence; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics / Q000378:metabolism; D054794:Glycomics / Q000379:methods*; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism*; D011134:Polysaccharides / Q000737:chemistry / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D037102:Lectins; D011134:Polysaccharides; D000217:Acyltransferases; C021802:2-acylglycerol O-acyltransferase; D005647:Fucosyltransferases; D017351:N-Acetylglucosaminyltransferases; C052254:alpha-1,6-mannosylglycoprotein beta 1,6-N-acetylglucosaminyltransferase; C020559:Glycoprotein 6-alpha-L-fucosyltransferase