title: Immunoglobulin G Fc N-glycan profiling in patients with gastric cancer by LC-ESI-MS: relation to tumor progression and survival.
abstract: The IgG Fc glycans strongly influence the Fcγ receptor interactions and Fc-mediated effector mechanisms. Changes in the structure of IgG glycans are associated with various diseases, such as infections and autoimmunity. However, the possible role of Fc glycans in tumor immunity is not yet fully understood. The aim of this study was to profile the Fc N-glycans of IgG samples from patients with gastric cancer (n = 80) and controls (n = 51) using LC-ESI-MS method to correlate the findings with stage of cancer and patients survival. Analysis of 32 different IgG N-glycans revealed significant increase of agalactosylated (GnGnF, GnGn(bi)F), and decrease of galactosylated (AGn(bi), AGn(bi)F, AA(bi), AAF) and monosialylated IgG glycoforms (NaAF, NaA(bi)) in cancer patients. A statistically significant increase of Fc fucosylation was observed in tumor stage II and III whereas reverse changes were found for the presence of bisecting GlcNAc. Higher level of fully sialylated glycans and elevated expression of glycans with bisecting GlcNAc were associated with better survival rate. Our findings provide the first evidence that the changes in Fc glycan profile may predict the survival of patients with gastric cancer. Cancer stage-dependent changes in Fc fucosylation and the bisecting N-acteylglucosamine expression as well as an association of several IgG glycoforms with the survival suggest that IgG glycosylation is related to pathogenesis of cancer and progression of the disease.
authors.affiliation: National Institute for Health Development, Hiiu, Tallinn, Estonia. kristel.kodar@tai.ee
authors.forename: Kristel
authors.initials: K
authors.lastname: Kodar
authors.forename: Johannes
authors.initials: J
authors.lastname: Stadlmann
authors.forename: Kersti
authors.initials: K
authors.lastname: Klaamas
authors.forename: Boris
authors.initials: B
authors.lastname: Sergeyev
authors.forename: Oleg
authors.initials: O
authors.lastname: Kurtenkov
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000097:blood*; D016022:Case-Control Studies; D002853:Chromatography, Liquid; D018450:Disease Progression; D005260:Female; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000097:blood* / Q000378:metabolism; D007074:Immunoglobulin G / Q000097:blood* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011134:Polysaccharides / Q000032:analysis* / Q000378:metabolism; D011379:Prognosis; D021241:Spectrometry, Mass, Electrospray Ionization; D013274:Stomach Neoplasms / Q000097:blood / Q000401:mortality* / Q000473:pathology*; D006023:Glycoproteins
chemical_list: D014408:Biomarkers, Tumor; D007141:Immunoglobulin Fc Fragments; D007074:Immunoglobulin G; D011134:Polysaccharides; C046179:glycosylated IgG; D006023:Glycoproteins