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利用 MALDI-TOF-MS 对甲状腺乳头状癌组织进行 N-糖链分析。

N-glycan profiling of papillary thyroid carcinoma tissues by MALDI-TOF-MS.

机构信息

Atatürk University, Faculty of Pharmacy, Department of Analytical Chemistry, 25240, Erzurum, Turkey.

Karabuk University, Faculty of Engineering, Department of Biomedical Engineering, 78000, Karabuk, Turkey.

出版信息

Anal Biochem. 2019 Nov 1;584:113389. doi: 10.1016/j.ab.2019.113389. Epub 2019 Aug 7.

DOI:10.1016/j.ab.2019.113389
PMID:31400301
Abstract

Papillary thyroid carcinoma (PTC) is a type of thyroid cancer whose incidence rate has increased recently all over the world. Glycosylation is a crucial post-translational modification (PTM) for the regulation of thyroid hormone synthesis in thyroid glands. However, our knowledge regarding the N-glycosylation change in PTC is limited. To the best of our knowledge, this is the first study to profile glycans in PTC tissues by mass spectrometry. Herein, we have analyzed the N-glycans of formalin-fixed paraffin-embedded (FFPE) tissues of patients diagnosed with PTC in a matched case-control study. Using MALDI-TOF(/TOF)-MS, 35 enzymatically released N-glycan compositions were characterized. The statistical analyses showed significant differences including six N-glycan compositions (p < 0.001) between patients and controls. It was determined that four of them (H5N4E1, H5N4F1E1, H5N4F1L1E1 and H5N4F1E2, E: α2,6-linked sialic acid; L: α2,3-linked sialic acid) were up-regulated in PTC tissues, whereas two N-glycans (H8N2 and H9N2) found to be down-regulated. Besides, a significant difference was found in six different N-glycan traits. Variants of PTC (follicular, classical, hurtle cell) were also studied to define specific N-glycan change for each variant.

摘要

甲状腺乳头状癌(PTC)是一种甲状腺癌,其发病率在全球范围内最近有所增加。糖基化是调节甲状腺激素合成的关键翻译后修饰(PTM)。然而,我们对 PTC 中 N-糖基化变化的了解有限。据我们所知,这是首次通过质谱法对 PTC 组织中的聚糖进行分析的研究。在此,我们通过基质辅助激光解吸电离飞行时间/飞行时间-质谱(MALDI-TOF(/TOF)-MS)分析了经福尔马林固定、石蜡包埋(FFPE)的 PTC 患者组织中的 N-糖链。共鉴定了 35 种酶切释放的 N-糖型组成。统计分析显示,患者与对照组之间存在 6 种 N-糖型组成(p<0.001)的显著差异。结果表明,其中 4 种 N-糖型(H5N4E1、H5N4F1E1、H5N4F1L1E1 和 H5N4F1E2,E:α2,6 连接的唾液酸;L:α2,3 连接的唾液酸)在 PTC 组织中上调,而两种 N-糖型(H8N2 和 H9N2)下调。此外,还发现了 6 种不同的 N-糖型特征存在显著差异。还研究了 PTC(滤泡型、经典型、Hurthle 细胞型)的变体,以确定每种变体的特定 N-糖基化变化。

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