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《工程(英文)》 >> 2023年 第26卷 第7期 doi: 10.1016/j.eng.2022.08.016

结直肠癌、基质和正常结肠黏膜显微解剖区域N-糖组的显著多样性

 a Center for Proteomics and Metabolomics, Leiden University Medical Center,  Leiden 2300 RC, the Netherlands

 b Copenhagen Center for Glycomics, Department of Cellular and Molecular Medicine, University of Copenhagen, Copenhagen 2200, Denmark

收稿日期: 2022-05-30 修回日期: 2022-08-05 录用日期: 2022-08-14 发布日期: 2022-11-12

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摘要

异常糖基化被认为是结直肠癌(CRC)的一个标志。虽然细胞系和血清的N-糖基化已经被广泛研究,但由于肿瘤的异质性和N-聚糖结构的复杂性,组织中肿瘤相关N-聚糖的分析受到阻碍。为了克服这些障碍,本文提出了一项使用激光捕获显微切割技术的研究,该研究可以在很大程度上分解来自异质性组织,包括癌细胞、间质细胞和健康黏膜细胞不同区域的不同N-糖组特征。采用多孔石墨化碳液相色谱-电喷雾电离串联质谱法对N-聚糖糖醇进行分析,实现了对同分异构体的分化和结构表征。总共鉴定出116 个N-聚糖,它们在癌症、间质和正常黏膜中呈现显著的表达差异。与健康黏膜相比,癌细胞显示α2-6 唾液酸化和单触角的N-聚糖增加,以及平分型N-聚糖减少。此外,特异性唾液酸化和携带(sialyl-)LewisA/X抗原的N-聚糖只在癌症中表达。与癌症相比,间质显示出较低水平的寡聚甘露糖苷和单触角N-聚糖、LewisA/X表位和硫酸盐化,以及(核心)岩藻糖基化和α2-3 唾液酸化表达的增加。本研究揭示了CRC和对照组织中不同细胞类型的不同N-糖组谱,并证明为发现癌症相关聚糖而对它们进行单独分析的必要性。

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