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通过糖组学鉴别甲状腺良恶性结节和甲状腺乳头状癌淋巴结转移

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

机构信息

Department of Medical Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, University of Utrecht, Utrecht, Netherlands.

出版信息

Front Endocrinol (Lausanne). 2021 Jun 25;12:692910. doi: 10.3389/fendo.2021.692910. eCollection 2021.

Abstract

BACKGROUND

Biomarkers are needed for patient stratification between benign thyroid nodules (BTN) and thyroid cancer (TC) and identifying metastasis in TC. Though plasma -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 -glycome of a TC cohort with regard to their applicability to serve as biomarkers.

METHODS

Plasma protein -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.

RESULTS

Plasma -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 -glycans and lymph node metastasis in TC, which added the accuracy of predicting metastasis before surgery to the existing method.

CONCLUSIONS

We comprehensively evaluated the plasma -glycomic changes in patients with TC or BTN for the first time. We determined several -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.

摘要

背景

需要生物标志物来对良性甲状腺结节(BTN)和甲状腺癌(TC)患者进行分层,并确定 TC 中的转移。尽管血浆糖组图谱在发现生物标志物方面显示出了潜力,并能为相关机制提供新的见解,但在 TC 和 BTN 中对此了解甚少。此外,有几项研究表明异常糖基化与 TC 之间存在关联。在这里,我们旨在探索 TC 患者的血浆蛋白糖组,以期将其作为生物标志物进行应用。

方法

使用基于 MALDI-TOF MS 的强大定量策略获得 TC、BTN 和匹配的健康对照(HC)的血浆蛋白糖组,并包含连接特异性唾液酸化信息。

结果

在主要糖基化特征(即复杂性、半乳糖基化、岩藻糖化和唾液酸化)方面,发现 BTN、TC 和 HC 之间的血浆糖组存在差异。连续降低 BTN 和 TC 的四个改变的聚糖特征,以及基于它们的分类模型显示出作为 BTN 和 TC 之间区分的高潜力的标志物(“中等准确”到“准确”)。此外,在 TC 中发现了血浆糖组与淋巴结转移之间的强烈关联,这增加了手术前预测转移的准确性。

结论

我们首次全面评估了 TC 或 BTN 患者的血浆糖组变化。我们确定了几种聚糖生物标志物,其中一些具有 TC 鉴别诊断的潜力,另一些可用于对 TC 患者进行低或高淋巴结转移风险分层。这些发现增强了对 TC 的理解。

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