Department of Laboratory Medicine, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, P.R. China.
Department of Surgery, University of Michigan Medical School, Ann Arbor, MI, USA.
Clin Chem Lab Med. 2019 Mar 26;57(4):407-416. doi: 10.1515/cclm-2018-0379.
Glycosylation is among the most important post-translational modifications for proteins and is of intrinsic complex character compared with DNAs and naked proteins. Indeed, over 50%-70% of proteins in circulation are glycosylated, and the "sweet attachments" have versatile structural and functional implications. Both the configuration and composition of the attached glycans affect the biological activities of consensus proteins significantly. Glycosylation is generated by complex biosynthetic pathways comprising hundreds of glycosyltransferases, glycosidases, transcriptional factors, transporters and the protein backbone. In addition, lack of direct genetic templates and glyco-specific antibodies such as those commonly used in DNA amplification and protein capture makes research on glycans and glycoproteins even more difficult, thus resulting in sparse knowledge on the pathophysiological implications of glycosylation. Fortunately, cutting-edge technologies have afforded new opportunities and approaches for investigating cancer-related glycosylation. Thus, glycans as well as aberrantly glycosylated protein-based cancer biomarkers have been increasingly recognized. This mini-review highlights the most recent developments in glyco-biomarker studies in an effort to discover clinically relevant cancer biomarkers using advanced analytical methodologies such as mass spectrometry, high-performance liquid chromatographic/ultra-performance liquid chromatography, capillary electrophoresis, and lectin-based technologies. Recent clinical-centered glycobiological studies focused on determining the regulatory mechanisms and the relation with diagnostics, prognostics and even therapeutics are also summarized. These studies indicate that glycomics is a treasure waiting to be mined where the growth of cancer-related glycomics and glycoproteomics is the next great challenge after genomics and proteomics.
糖基化是蛋白质最重要的翻译后修饰之一，与 DNA 和裸蛋白相比，具有内在的复杂特征。事实上，循环中超过 50%-70%的蛋白质都发生了糖基化，这些“甜蜜的附着物”具有多样的结构和功能意义。连接糖的构型和组成都显著影响共识蛋白的生物活性。糖基化是由包含数百种糖基转移酶、糖苷酶、转录因子、转运蛋白和蛋白质骨架的复杂生物合成途径产生的。此外，由于缺乏直接的遗传模板和糖基特异性抗体，如常用于 DNA 扩增和蛋白质捕获的抗体，使得对聚糖和糖蛋白的研究更加困难，因此对糖基化的病理生理意义的了解仍然有限。幸运的是，前沿技术为研究与癌症相关的糖基化提供了新的机会和方法。因此，聚糖以及异常糖基化的基于蛋白质的癌症生物标志物越来越受到关注。本综述重点介绍了糖基生物标志物研究的最新进展，努力使用质谱、高效液相色谱/超高效液相色谱、毛细管电泳和基于凝集素的技术等先进分析方法来发现具有临床相关性的癌症生物标志物。还总结了最近以临床为中心的糖生物学研究，重点研究了调节机制及其与诊断、预后甚至治疗的关系。这些研究表明，糖组学是一个有待挖掘的宝库，在癌症相关糖组学和糖蛋白质组学的发展之后，基因组学和蛋白质组学的下一个重大挑战是糖生物学。
