title: Quantitative analysis of serum IgG galactosylation assists differential diagnosis of ovarian cancer.
abstract: CA-125, the most frequently used biomarker for ovarian cancer detection, cannot provide accurate diagnosis due to its poor specificity as it may also increase in many benign gynecological conditions. Thus, reducing the false-positive outcomes is urgently needed. Decrease in terminal galactosylated N-glycans of serum IgG has been found in various malignancies compared to healthy controls. Here, this alteration of IgG galactosylation was extended to be investigated between ovarian cancer and benign conditions with similar elevated CA-125 levels, in an attempt to effectively distinguish between false-positive subjects and ovarian cancer patients. In the study of 58 patients with elevated CA-125 levels (>35 U/mL), the degree of IgG galactosylation was measured from the relative intensities of IgG digalactosyl (G2), monogalactosyl (G1), and agalactosylated (G0) N-glycans according to the formula G0/(G1+G2·2). This ratio was found significantly higher in the malignant group than in the benign group (0.74 vs 0.34; p<0.0001). ROC analysis demonstrated an improved specificity from 65.2% (by CA-125 test alone) to 84.6%, while maintaining sensitivity at 90% by incorporating quantitative analysis of IgG galactosylation in the current assay. The results suggest that combining quantitative alteration of IgG galactosylation with CA-125 may generate an overall more robust approach for differential diagnosis of ovarian cancer.
authors.affiliation: Key Laboratory of Glycoconjugate Research Ministry of Public Health, Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Institute of Biomedical Sciences, Fudan University, Shanghai, PR China.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Qian
authors.forename: Yisheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Xingwang
authors.initials: X
authors.lastname: Zhang
authors.forename: Lei
authors.initials: L
authors.lastname: Zhou
authors.forename: Zejian
authors.initials: Z
authors.lastname: Zhang
authors.forename: Jiejie
authors.initials: J
authors.lastname: Xu
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Ruan
authors.forename: Shifang
authors.initials: S
authors.lastname: Ren
authors.forename: Congjian
authors.initials: C
authors.lastname: Xu
authors.forename: Jianxin
authors.initials: J
authors.lastname: Gu
mesh_terms: D000328:Adult; D019540:Area Under Curve; D014408:Biomarkers, Tumor / Q000097:blood*; D018394:CA-125 Antigen / Q000097:blood; D002236:Carbohydrate Conformation; D002240:Carbohydrate Sequence; D016022:Case-Control Studies; D003937:Diagnosis, Differential; D005260:Female; D005690:Galactose / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood*; D008875:Middle Aged; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis*; D011499:Protein Processing, Post-Translational; D012372:ROC Curve; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
chemical_list: D014408:Biomarkers, Tumor; D018394:CA-125 Antigen; D007074:Immunoglobulin G; D005690:Galactose