BackgroundThe　relationship　between　cancer　development　and　alterations　in　IgG　N-glycosylation　has　been　well-established.　However,　comprehensive　profiling　of　the　N-glycome　and　N-glycoproteome　in　gastric　cancer　(GC)　remains　limited.　Furthermore,　the　prognostic　potential　of　IgG　N-glycan　patterns　in　identifying　precursors　to　GC　has　yet　to　be　fully　elucidated.MethodsThe　IgG　N-glycome　in　GC　was　characterized　using　a　custom　high-throughput　orthogonal　mass　spectrometry　approach.　Multivariate　analysis　was　employed　to　identify　and　assess　glycomic　alterations.　A　comprehensive　bioinformatics　analysis　was　also　conducted　to　investigate　the　differential　expression　of　N-glycosylation-related　genes　and　their　potential　roles　in　GC　pathogenesis.　Additionally,　interleukin-11　(IL-11)　levels　were　quantified　using　a　standardized　enzyme-linked　immunosorbent　assay　(ELISA).ResultsGalactosylation　and　sialylation　of　IgG　decreased　mainly　in　the　IgG1　and　IgG2　subclasses　in　GC,　with　subclass-specific　changes　in　IgG3　and　IgG4　galactosylation.　These　glycan　modifications　were　represented　by　unique　glycopeptides　(IgG1_H5N5,　IgG2_H4N3F1,　IgG2_H4N4,　IgG2_H4N4F1S1,　IgG3/4_H4N4F1,　IgG3/4_H4N4F1S1),　which　outperformed　CA72-4　for　GC　diagnosis.　Analysis　of　key　glycogenes　revealed　differential　expression　patterns,　implicating　a　functional　role　for　IgG　N-glycosylation　in　GC.　Notably,　the　abundance　of　specific　IgG　glycosylation　exhibited　a　significant　correlation　with　serum　level　of　IL-11.ConclusionsAlterations　in　subclass-specific　IgG　N-glycosylation　represent　promising　biomarkers　for　the　detection　and　monitoring　of　GC　progression,　potentially　influenced　by　cytokine-driven　inflammation.　Understanding　these　changes　could　improve　our　knowledge　of　molecular　mechanisms,　aiding　in　diagnostic　improvements　and　therapeutic　development.