title: Glycoproteomic Analysis of Malignant Ovarian Cancer Ascites Fluid Identifies Unusual Glycopeptides.
abstract: 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.
authors: Division of Hematology and Oncology, Department of Internal Medicine, UC Davis School of Medicine , Sacramento, California 95817, United States.
authors: Suzanne
authors: S
authors: Miyamoto
authors: Department of Chemistry, UC Davis , Davis, California 95616, United States.
authors: L Renee
authors: LR
authors: Ruhaak
authors: Division of Hematology and Oncology, Department of Internal Medicine, UC Davis School of Medicine , Sacramento, California 95817, United States.
authors: Carol
authors: C
authors: Stroble
authors: Proteomic Core, Genome Center, UC Davis , Davis, California 95616, United States.
authors: Michelle R
authors: MR
authors: Salemi
authors: Proteomic Core, Genome Center, UC Davis , Davis, California 95616, United States.
authors: Brett
authors: B
authors: Phinney
authors: Department of Chemistry, UC Davis , Davis, California 95616, United States.
authors: Carlito B
authors: CB
authors: Lebrilla
authors: Division of Gynecologic Oncology, UC Davis Medical Center , Sacramento, California 95817, United States.
authors: Gary S
authors: GS
authors: Leiserowitz
mesh_terms: D001202:Ascitic Fluid / Q000737:chemistry*; D018394:CA-125 Antigen / Q000032:analysis; D005260:Female; D005353:Fibronectins / Q000032:analysis; D054794:Glycomics; D006020:Glycopeptides / Q000032:analysis*; D006023:Glycoproteins; D006801:Humans; D037102:Lectins / Q000378:metabolism; D018396:Mucin-1 / Q000032:analysis; D010051:Ovarian Neoplasms / Q000737:chemistry*; D011134:Polysaccharides / Q000378:metabolism; D040901:Proteomics / Q000379:methods
chemical_list: D018394:CA-125 Antigen; D005353:Fibronectins; D006020:Glycopeptides; D006023:Glycoproteins; D037102:Lectins; C060192:MUC1 protein, human; D018396:Mucin-1; D011134:Polysaccharides
keywords: N-glycans; glycopeptides; glycoproteomics; malignant ascites; mass spectrometry; ovarian cancer; proteomics