title: Protein-Specific Differential Glycosylation of Immunoglobulins in Serum of Ovarian Cancer Patients.
abstract: Previous studies indicated that glycans in serum may serve as biomarkers for diagnosis of ovarian cancer; however, it was unclear to which proteins these glycans belong. We hypothesize that protein-specific glycosylation profiles of the glycans may be more informative of ovarian cancer and can provide insight into biological mechanisms underlying glycan aberration in serum of diseased individuals. Serum samples from women diagnosed with epithelial ovarian cancer (EOC, n = 84) and matched healthy controls (n = 84) were obtained from the Gynecologic Oncology Group. Immunoglobulin (IgG, IgA, and IgM) concentrations and glycosylation profiles were quantified using multiple reaction monitoring mass spectrometry. Differential and classification analyses were performed to identify aberrant protein-specific glycopeptides using a training set. All findings were validated in an independent test set. Multiple glycopeptides from immunoglubins IgA, IgG, and IgM were found to be differentially expressed in serum of EOC patients compared with controls. The protein-specific glycosylation profiles showed their potential in the diagnosis of EOC. In particular, IgG-specific glycosylation profiles are the most powerful in discriminating between EOC case and controls. Additional studies of protein- and site-specific glycosylation profiles of immunoglobulins and other proteins will allow further elaboration on the characteristics of biological functionality and causality of the differential glycosylation in ovarian cancer and thus ultimately lead to increased sensitivity and specificity of diagnosis.
authors.affiliation: Department of Chemistry, University of California , Davis, California 95616, United States.
authors.forename: L Renee
authors.initials: LR
authors.lastname: Ruhaak
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of California , Davis, California 95616, United States.
authors.forename: Kyoungmi
authors.initials: K
authors.lastname: Kim
authors.affiliation: Department of Chemistry, University of California , Davis, California 95616, United States.|University of California Davis Medical Center , Sacramento, California 95817, United States.
authors.forename: Carol
authors.initials: C
authors.lastname: Stroble
authors.affiliation: Division of Biostatistics, Department of Public Health Sciences, University of California , Davis, California 95616, United States.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Taylor
authors.affiliation: Department of Chemistry, University of California , Davis, California 95616, United States.
authors.forename: Qiuting
authors.initials: Q
authors.lastname: Hong
authors.affiliation: University of California Davis Medical Center , Sacramento, California 95817, United States.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Miyamoto
authors.affiliation: Department of Chemistry, University of California , Davis, California 95616, United States.
authors.forename: Carlito B
authors.initials: CB
authors.lastname: Lebrilla
authors.affiliation: University of California Davis Medical Center , Sacramento, California 95817, United States.|Division of Gynecologic Oncology, University of California Davis Medical Center , Sacramento, California 98517, United States.
authors.forename: Gary
authors.initials: G
authors.lastname: Leiserowitz
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D006020:Glycopeptides / Q000097:blood*; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D009375:Neoplasms, Glandular and Epithelial / Q000097:blood* / Q000175:diagnosis; D010051:Ovarian Neoplasms / Q000097:blood* / Q000175:diagnosis; D012372:ROC Curve; D006023:Glycoproteins
chemical_list: D014408:Biomarkers, Tumor; D006020:Glycopeptides; D007074:Immunoglobulin G; C046179:glycosylated IgG; D006023:Glycoproteins
keywords: N-glycosylation; biomarker; immunoglobulin; ovarian cancer; serum
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