Nomograms Based on Serum N-glycome for Diagnosis of Papillary Thyroid Microcarcinoma and Prediction of Lymph Node Metastasis

Non-invasive biomarkers for the diagnosis and prognosis of papillary thyroid microcarcinoma (PTMC) are still urgently needed. We aimed to characterize the N-glycome of PTMC, and establish nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). N-glycome of PTMC (LNM vs. non-LNM, capsular invasion (CI) vs. non-CI (NCI)) and matched healthy controls (HC) were quantitatively analyzed based on mass spectrometry. N-glycan traits associated with PTMC/LNM were used to create binomial logistic regression models and were visualized as nomograms. We found serum N-glycome differed between PTMC and HC in high-mannose, complexity, fucosylation, and bisection, of which, four N-glycan traits (TM, CA1, CA4, and A2Fa) were significantly associated with PTMC. The nomogram based on four traits achieved good performance for the identification of PTMC. Two N-glycan traits (CA4 and A2F0S0G) showed strong associations with LNM. The nomogram based on two traits showed relatively good performance in predicting LNM. We also found differences between CI and NCI in several N-glycan traits, which were not the same as that associated with LNM. This study reported serum N-glycosylation signatures of PTMC for the first time. Nomograms constructed from aberrant glycans could be useful tools for PTMC diagnosis and stratification.

Automated summary

This study characterized the N-glycome of papillary thyroid microcarcinoma (PTMC), and established nomograms for the diagnosis of PTMC and the prediction of lymph node metastasis (LNM). The study found significant differences in serum N-glycome between PTMC and healthy controls, as well as associations between certain N-glycan traits and PTMC and LNM. Nomograms based on these traits showed good performance in the identification of PTMC and the prediction of LNM.