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Background  Novel biomarkers are urgently needed to distinguish between benign and malignant thyroid nodules and detect thyroid cancer in the early stage. The associations between serum IgG N-glycosylation and thyroid cancer risk have been revealed. We aimed to explore the potential of IgG N-glycan traits as biomarkers in the differential diagnosis of thyroid cancer.    Methods  Plasma IgG N-glycome analysis was applied to a discovery cohort followed by independent validation. IgG N-glycan profiles were obtained using a robust quantitative strategy based on matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. IgG N-glycans were relatively quantified, and classification performance was evaluated based on directly detected and derived glycan traits.    Results  Four directly detected glycans were significantly changed in thyroid cancer patients compared to that in non-cancer controls. Derived glycan traits and a classification glycol-panel were generated based on the directly detected glycan traits. In the discovery cohort, derived trait BN (bisecting type neutral N-glycans) and the glyco-panel showed potential in distinguishing between thyroid cancer and non-cancer controls with AUCs of 0.920 and 0.917, respectively. The diagnostic potential was further validated. Derived trait BN and the glycol-panel displayed “accurate” performance (AUC>0.8) in discriminating thyroid cancer from benign thyroid nodules and healthy controls in the validation cohort. Meanwhile, derived trait BN and the glycol-panel also showed diagnostic potential in detecting early-stage thyroid cancer.    Conclusions  IgG N-glycome analysis revealed N-glycomic differences that allow classification of thyroid cancer from non-cancer controls. Our results suggested that derived trait BN and the classification glyco-panel rather than single N-glycans may serve as candidate biomarkers for further validation.

Diagnostic Potential of Plasma IgG N-glycans in Discriminating Thyroid Cancer from Benign Thyroid Nodules and Healthy Controls