Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies Unusual Glycopeptides

Ovarian cancer is a major cause of cancer mortality among women, largely due to late diagnosis of advanced metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins, especially glycosylation that is particula...

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Bibliographic Details
Published in:Journal of proteome research 2016-09, Vol.15 (9), p.3358-3376
Main Authors: Miyamoto, Suzanne, Ruhaak, L. Renee, Stroble, Carol, Salemi, Michelle R, Phinney, Brett, Lebrilla, Carlito B, Leiserowitz, Gary S
Format: Article
Language:English
Subjects:
Ascitic Fluid - chemistry
CA-125 Antigen - analysis
Female
Fibronectins - analysis
Glycomics
Glycopeptides - analysis
Glycoproteins
Humans
Lectins - metabolism
Mucin-1 - analysis
Ovarian Neoplasms - chemistry
Polysaccharides - metabolism
Proteomics - methods
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Summary:Ovarian cancer is a major cause of cancer mortality among women, largely due to late diagnosis of advanced metastatic disease. More extensive molecular analysis of metastatic ovarian cancer is needed to identify post-translational modifications of proteins, especially glycosylation that is particularly associated with metastatic disease to better understand the metastatic process and identify potential therapeutic targets. Glycoproteins in ascites fluid were enriched by affinity binding to lectins (ConA or WGA) and other affinity matrices. Separate glycomic, proteomic, and glycopeptide analyses were performed. Relative abundances of different N-glycan groups and proteins were identified from ascites fluids and a serum control. Levels of biomarkers CA125, MUC1, and fibronectin were also monitored in OC ascites samples by Western blot analysis. N-Glycan analysis of ascites fluids showed the presence of large, highly fucosylated and sialylated complex and hybrid glycans, some of which were not observed in normal serum. OC ascites glycoproteins, haptoglobin, fibronectin, lumican, fibulin, hemopexin, ceruloplasmin, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were more abundant in OC ascites or not present in serum control samples. Further glycopeptide analysis of OC ascites identified N- and O-glycans in clusterin, hemopexin, and fibulin glycopeptides, some of which are unusual and may be important in OC metastasis.
ISSN:1535-3893
1535-3907
DOI:10.1021/acs.jproteome.6b00548