Department of Chemistry, Beijing Key Laboratory of Microanalytical Methods and Instrumentation, Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Tsinghua University, Beijing, 100084, China.
Anal Bioanal Chem. 2022 Jul;414(18):5617-5626. doi: 10.1007/s00216-022-04010-w. Epub 2022 Mar 23.
As one of the most important post-translational modifications, protein glycosylation plays vital role in various physiological processes. With multitudinous glycosyltransferases, N-glycans present structural diversity in linkages and branching styles. Structure-specific glycan profiling may provide more potential biological information than compositional profiling. In this work, N-glycans released from human serum samples were derivatized with reduction and methylamination prior to profiling using nanoLC-ESI-MS with PGC as stationary phase. In addition, α 2-3 neuraminidase was also applied for distinguishing the linkage types of sialic acid corresponding to different isomers. Relative abundances of 280 isomeric N-glycans were compared and 20 isomers showed significant difference between multiple myeloma cases and healthy controls. ROC was performed to assess the significantly altered isomeric glycans and 6 AUCs have exceeded 0.80, providing high diagnostic accuracy for MM. PCA is also employed to establish the differences among sample sets. Furthermore, these specific isomers have also been used for early detection of multiple myeloma, presenting important clinical application value. Isomer-specific biomarker discovery in multiple myeloma with dual-derivatized N-glycans.
作为最重要的翻译后修饰之一，蛋白质糖基化在各种生理过程中起着至关重要的作用。由于存在多种糖基转移酶，N-聚糖在连接方式和分支方式上呈现出结构多样性。结构特异性聚糖分析可能比组成分析提供更多潜在的生物学信息。在这项工作中，用人血清样品中的 N-糖链在进行分析之前，先用还原和甲胺化进行衍生化，然后用 PGC 作为固定相进行纳升液相色谱-电喷雾-质谱分析。此外，α 2-3 神经氨酸酶也被用于区分不同异构体中对应于不同异构体的唾液酸的连接类型。比较了 280 个异构 N-聚糖的相对丰度，20 个异构体在多发性骨髓瘤病例和健康对照之间存在显著差异。ROC 用于评估显著改变的异构体糖，并 6 个 AUC 超过 0.80，为 MM 提供了高诊断准确性。PCA 也用于建立样本集之间的差异。此外，这些特定的异构体也已用于多发性骨髓瘤的早期检测，具有重要的临床应用价值。双衍生化 N-聚糖在多发性骨髓瘤中的异构体特异性生物标志物发现。
