Serum immunoglobulin G N-glycome: a potential biomarker in endometrial cancer

Background: With the increase in incidence and mortality of endometrial cancer (EC), there is an urgent need to explore non-invasive strategies for identifying EC patients and facilitating risk stratification. The alteration of immunoglobulin G (IgG) N-glycome has been indicated in autoimmune diseases and several cancer types, demonstrating a significant association with disease pathogenesis and progression. However, little has been investigated in the IgG N-glycome of EC patients. Methods: A total of 94 EC patients and 112 healthy females were recruited and sorted into an EC cohort and a control cohort. Serum samples were obtained from every participant, and IgG N-glycome profiling was conducted using ultra-performance liquid chromatography (UPLC). Results: A total of 24 directly measured N-glycans and 11 derived traits based on the shared glycan structures were analyzed in the EC and control cohorts. We detected a significant downregulation of galactosylation and sialylation in the EC cohort compared with the control cohort, while glycans with bisecting N-acetylglucosamine ( GlcNAc) were elevated in EC patients. Receiver operating characteristic (ROC) analysis based on glycan traits showed good diagnostic performance of IgG N-glycans for EC. Furthermore, by exploring the association of IgG N-glycome with prognostic risk factors in EC, we observed that lower levels of galactosylation and sialylation were correlated with high-risk factors including older age, non-endometrioid histologic subtypes, advanced stage, poor differentiation of tumor, and >50% myometrial invasion (MI). Conclusions: Our results suggest that the IgG N-glycome profile could be a potential biomarker for EC diagnosis and a promising indicator for prognostic risk factors, and thus may facilitate the early detection of EC and the identification of high-risk patients.