title: Disease-specific IgG Fc N-glycosylation as personalized biomarkers to differentiate gastric cancer from benign gastric diseases.
abstract: Interest in the pathophysiological role of IgG fragment crystallizable (Fc) N-linked glycosylation arose from changes in humoral immune responses. In this study, circulating disease-specific IgG (DSIgG) derived from serum immunoinflammation-related protein complexes was isolated from 846 serum samples of 443 patients with benign gastric diseases (BGDs) and 403 patients with gastric cancer (GC), and DSIgG glycopeptides attached to IgG Fc region at the site of Asn297 were analyzed using matrix-assisted laser desorption/ionization- Fourier transform ion cyclotron resonance mass spectrometry (MALDI-FTICR MS). A total of 22 glycopeptides were detected. Statistical analysis indicated that DSIgG1 G1S, DSIgG2 G0F, G1, G2F, and G2FS as well as DSIgG2 galactosylation and sialylation are significantly associated with sex in BGD patients and that the age-specific glycoforms and glycosylation features from DSIgG between BGD patients and GC patients have similar change trends. In addition, significant changes in galactosylation, sialylation, and bisecting N-acetylglucosamine (GlcNAc) from DSIgG were also observed between two pathophysiological states. Receiver operating characteristic (ROC) analysis indicated that the G2FN/G1FN (from DSIgG2) ratio has an excellent capability to distinguish female BGD patients from female GC patients over the age range of 20-79 years, with the sensitivity of 82.6%, the specificity of 82.6%, and the area under curve (AUC) of 0.872.
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Clinical Laboratory, Heze Municipal Hospital, Shandong 274031, P.R. China.
authors.forename: Bingchao
authors.initials: B
authors.lastname: Chen
authors.affiliation: Department of Clinical Laboratory, Heze Municipal Hospital, Shandong 274031, P.R. China.
authors.forename: Yanmin
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Oncology Surgery, First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, 710061, P.R. China.
authors.forename: Peng
authors.initials: P
authors.lastname: Xia
authors.affiliation: Laboratory Medicine Center, China-Japan Union Hospital of Jilin University, Changchun, 130041, P.R. China.
authors.forename: Chengyan
authors.initials: C
authors.lastname: He
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Ruiqing
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Mo
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Biophysics and Structural Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and School of Basic Medicine, Peking Union Medical College, Beijing 100005, P.R. China.
authors.forename: Zhili
authors.initials: Z
authors.lastname: Li
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001216:Asparagine / Q000737:chemistry; D014408:Biomarkers, Tumor / Q000097:blood / Q000737:chemistry*; D005260:Female; D006031:Glycosylation; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000097:blood / Q000737:chemistry*; D007074:Immunoglobulin G / Q000097:blood*; D008297:Male; D008875:Middle Aged; D057285:Precision Medicine; D012372:ROC Curve; D012680:Sensitivity and Specificity; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013274:Stomach Neoplasms / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D001216:Asparagine