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

Abstract

BackgroundNovel 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.MethodsPlasma 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.ResultsFour 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.ConclusionsIgG 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.

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

“…Detailed information on the glycan release and derivatization process is provided in the Supplementary Materials . The derivatized N -glycans were then purified by hydrophilic interaction liquid chromatography solid-phase extraction (HILIC-SPE) micro-tips, and were eventually eluted with MilliQ water according to the previously reported method [ 26 , 29 , 30 ]. Thereafter, 1 μL of purified glycans were mixed with 1 μL of the matrix (5 mg/mL super-2,5-dihydroxybenzoic acid in 50% acetonitrile with 1 mM NaOH) on a target plate and were air-dried at room temperature.…”

“…The raw MS data were processed according to the workflow reported in the previous study [ 28 , 29 , 30 ]. The raw MS data had been deposited in GlycoPOST (ID: GPST000252, accessed on 22 August 2022) [ 31 ].…”

“…The following supporting information are available online: , Table S1: The general view of directly detected glycans; Table S2: Description and calculation of derived glycan traits; Table S3: Data quality control; Table S4: Derived N -glycan trait changes in the cohort. References [ 25 , 26 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ] are cited in the supplementary materials.…”

Serum IgG N‐glycans enable early detection and early relapse prediction of colorectal cancer

“…These efforts not only further improve molecular therapy but also provide more effective biomarkers for early diagnosis and prognosis. 3,4 CRC mostly develops from advanced adenomas (AA), which are considered precancerous lesions with a high risk of carcinogenesis. 5 Timely and accurate identification of precancerous lesions of CRC has important clinical significance.…”

“…Therefore, multiple risk factors for CRC, including environmental, genetic and posttranslational modifications (PTMs), have attracted the attention of numerous research teams. These efforts not only further improve molecular therapy but also provide more effective biomarkers for early diagnosis and prognosis 3,4 …”