Background:Gastric cancer (GC) is one of the most aggressive gastrointestinal malignancy and leading cause of cancer related deaths worldwide,warranting the urgent discovery of biomarkers for early detection. IgG glycosylation is strongly related to disease progression and specific IgG glycans have been regarded as the next-generation biomarker, whereas it is rarly studied on the association between subclass-specific IgG glycosylation profile and GC progression. Methods:A total of 141 individuals were enrolled and randomly sorted into discovery set consisting of normal (N=30) and cancer patients (N=20), and validation set including controls (N=30), benign (N=25) and cancer (N=36).IgG glycopeptides were tryptic digested and enrichmed by microcrystalline cellulose based solid phase extraction.Subclass-specific IgG N-glycosylation was analyzed by nanoLC-MS/MS. Results:It was found that GC progression was associated with increased sialylation and decreased bisection of IgG2, as well as substantially decreased sialylation of IgG1 and increased galactosylation of IgG3/4.Further analysis of individual glycopeptides showed the changes of particular glycosylation of IgGwere reflected by the specific glycans taht could apparently distinguish different stages of gastric disease patients from normal. Conclusions:Different subclasses of IgG glycosylation were differentially expressed in GC, specific IgG glycopeptides could be promising biomarker for early detection of GC patients.