Abstract
BACKGROUND: The 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. METHODS: The 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). RESULTS: Galactosylation 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. CONCLUSIONS: Alterations 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.