N-glycosylation of serum proteins for the assessment of patients with IgD multiple myeloma

Abstract

Background: Because glycosylation is one of the most common post-translational modifications of proteins and because changes in glycosylation have been shown to have a significant correlation with the development of many cancer types, we investigated the serum N-glycome used to diagnose, stage and evaluate the pathological outcomes in IgD multiple myeloma. Methods: Serum samples were available for 20 patients with IgD multiple myeloma, 41 patients with light chain multiple myeloma and 42 healthy control subjects. Serum N-glycans were released and analysed using DNA sequencer-assisted fluorophore-assisted capillary electrophoresis. Results: Characteristic changes were revealed in the serum N-glycome of IgD myeloma. In particular, three N-glycans (NG1(6)A2F, Peak3; NG1(3)A2F, Peak4; NA2FB, Peak7) showed increased clinical value. The best area under the ROC curve of NG1(6)A2F to diagnose IgD myeloma was 0.981, with a 95.0% sensitivity and 95.2% specificity, and that of NG1(3)A2F was 0.936, with a 95.0% sensitivity and 78.6% specificity. The best area under the ROC curve of NA2FB/NG1(3)A2F to differentially diagnose IgD myeloma versus light chain myeloma was 0.744, with a 95.3% sensitivity and 50.0% specificity. The level of NG1(3)A2F was correlated with the international staging system, while the higher abundance of NA2FB presented in IgD myeloma was predictive of a shorter progression-free survival. Conclusions: The advent of serum N-glycan signatures may play a role in the diagnosis, staging and prognosis of IgD myeloma and will serve as the foundation for a precision medicine approach to this rare subtype of multiple myeloma.