Distinguishing Benign and Malignant Thyroid Nodules and Identifying Lymph Node Metastasis in Papillary Thyroid Cancer by Plasma N-Glycomics

Abstract

BackgroundBiomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma N-glycome profiling has shown potential in the discovery of biomarkers and can provide new insight into the mechanisms involved, little is known about it in TC and BTN. Besides, several studies have indicated associations between abnormal glycosylation and TC. Here, we aimed to explore plasma protein N-glycome of a TC cohort with regard to their applicability to serve as biomarkers.MethodsPlasma protein N-glycomes of TC, BTN, and matched healthy controls (HC) were obtained using a robust quantitative strategy based on MALDI-TOF MS and included linkage-specific sialylation information.ResultsPlasma N-glycans were found to differ between BTN, TC, and HC in main glycosylation features, namely complexity, galactosylation, fucosylation, and sialylation. Four altered glycan traits, which were consecutively decreased in BTN and TC, and classification models based on them showed high potential as biomarkers for discrimination between BTN and TC (“moderately accurate” to “accurate”). Additionally, strong associations were found between plasma N-glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method.ConclusionsWe comprehensively evaluated the plasma N-glycomic changes in patients with TC or BTN for the first time. We determined several N-glycan biomarkers, some of them have potential in the differential diagnosis of TC, and the others can help to stratify TC patients to low or high risk of lymph node metastasis. The findings enhanced the understanding of TC.

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

“…The peaks of MS spectra were manually assigned to N -glycan compositions using the GlycoPeakfinder tool of GlycoWorkbench [ 33 , 34 ]. The N -glycan compositions were also confirmed by previous literature [ 25 , 28 , 29 ]. A detailed process for glycan identification is provided in the Supplementary Materials .…”

“…Aberrant N -glycans in PTC patients (compared to HC) discovered in our previous study [ 25 ] and dysregulated N -glycans in PTMC patients (compared to HC) found in the present study were compared. We found three glycan traits (CA4, CFa, and A2Fa) were both dysregulated in PTC and PTMC.…”

“…Moreover, we screened out four potential diagnostic biomarkers for PTMC (TM, CA1, CA4, and A2Fa) in the present study ( Figure 2 and Figure 4 ). Two of them (TM and CA1) are specific diagnostic biomarkers for PTMC, whereas the left two (CA4 and A2Fa) were also found useful in PTC diagnosis in our previous study [ 25 ].…”

“…Furthermore, serological glycomic profiling is a rising non-invasion approach for the discovery of potential biomarkers for cancer diagnosis and disease surveillance in recent years [ 23 , 24 ]. A growing body of studies suggests that total serum/plasma N -glycome has great potential as a biomarker for the diagnosis of cancers, including PTC [ 25 , 26 , 27 ]. In response to the current controversy over whether the pathological mechanisms of PTMC and PTC are the same, we conduct this PTMC glycomics study on the basis of our previous PTC glycomic study [ 25 ], hoping to provide new clues for their pathological mechanism and find PTMC-specific diagnostic biomarkers.…”

“…A growing body of studies suggests that total serum/plasma N -glycome has great potential as a biomarker for the diagnosis of cancers, including PTC [ 25 , 26 , 27 ]. In response to the current controversy over whether the pathological mechanisms of PTMC and PTC are the same, we conduct this PTMC glycomics study on the basis of our previous PTC glycomic study [ 25 ], hoping to provide new clues for their pathological mechanism and find PTMC-specific diagnostic biomarkers. Moreover, whether serum N -glycome has potential as a biomarker for predicting LNM of PTMC still needs to be investigated.…”