The Key Laboratory for Biomedical Photonics of MOE at Wuhan National Laboratory for Optoelectronics - Hubei Bioinformatics & Molecular Imaging Key Laboratory, Systems Biology Theme, Department of Biomedical Engineering, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan 430074, China.
Department of Laboratory Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
J Proteomics. 2018 Jun 15;181:160-169. doi: 10.1016/j.jprot.2018.04.016. Epub 2018 Apr 16.
Glycosylation is one of the most important post-translational modifications of protein. Recently, global profiling of human serum glycomics has become a noninvasive method for cancer-related biomarker discovery and many studies have focused on compositional glycan profiling. In contrast, structure-specific glycan profiling may provide more potential biomarkers with higher specificity than compositional profiling. In this work, N-glycans released from human serum were neutralized with methylamine and reduced by ammonia-borane complex prior to profiling using nanoLC-ESI-MS with porous graphitized carbon (PGC) and relative abundances of over 280 isomers were compared between pancreatic cancer (PC) cases (n = 32) and healthy controls (n = 32). Statistical analysis identified 25 specific-isomeric biomarkers with significant differences (p-value < 0.05). ROC and PCA analysis were performed to assess the potential biomarkers which were identified as being significantly altered in cancer. The AUCs of the significantly changed specific-isomers were ranging from 0.712 to 0.949. In addition, with the combination of all potential biomarkers, a higher AUC of 0.976 with sensitivity (93.5%) and specificity (90.6%) was obtained. Overall, the proposed strategy coupled to relative quantitative analysis of isomeric glycans make it possible to discover new biomarkers for the diagnosis of PC.
Pancreatic cancer (PC) has a poor prognosis with a five-year survival rate <5%. Therefore, a strategy for accurate diagnosis of PC is indeed required. In this paper, a dual-derivatized strategy for structure-specific glycan profiling has been used and according to our best knowledge, this is the first application of this strategy for PC biomarker discovery, in which the separation, identification and relative quantification of isomeric glycans can be simultaneously obtained. In addition, by in-depth analysis of isomeric glycans, the full description of the stereo- and region- diversity of glycans can also be achieved, which might provide more potential information for PC biomarker discovery.
糖基化是蛋白质翻译后修饰中最重要的一种。最近，人类血清糖组学的全局分析已成为癌症相关生物标志物发现的一种非侵入性方法，许多研究都集中在组成性糖谱分析上。相比之下，结构特异性糖谱分析可能比组成性分析提供更多具有更高特异性的潜在生物标志物。在这项工作中，用甲胺将人血清中的 N-糖基中和，并在使用多孔石墨化碳（PGC）的 nanoLC-ESI-MS 进行分析之前用氨硼烷复合物还原，在胰腺癌（PC）病例（n=32）和健康对照组（n=32）之间比较了超过 280 种异构体的相对丰度。统计分析确定了 25 种具有显著差异的特异性同型生物标志物（p 值<0.05）。进行 ROC 和 PCA 分析以评估在癌症中被鉴定为显著改变的潜在生物标志物。显著改变的特异性同型物的 AUC 范围为 0.712 至 0.949。此外，通过组合所有潜在的生物标志物，获得了更高的 AUC（0.976），具有 93.5%的敏感性和 90.6%的特异性。总体而言，所提出的策略与异构糖的相对定量分析相结合，为 PC 的诊断发现新的生物标志物成为可能。
胰腺癌（PC）的预后较差，五年生存率<5%。因此，确实需要一种准确诊断 PC 的策略。在本文中，使用了一种双衍生化策略进行结构特异性糖谱分析，据我们所知，这是该策略首次应用于 PC 生物标志物发现，其中可以同时获得异构糖的分离、鉴定和相对定量。此外，通过对异构糖的深入分析，还可以实现糖的立体和区域多样性的全面描述，这可能为 PC 生物标志物发现提供更多潜在信息。
