Mereiter Stefan, Balmaña Meritxell, Gomes Joana, Magalhães Ana, Reis Celso A
Instituto de Investigação e Inovação em Saúde (I3S), University of Porto, Porto, Portugal; Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP), Porto, Portugal; Institute of Biomedical Sciences of Abel Salazar (ICBAS), University of Porto, Porto, Portugal.
Biochemistry and Molecular Biology Unit, Department of Biology, University of Girona , Girona , Spain.
Front Oncol. 2016 Mar 9;6:55. doi: 10.3389/fonc.2016.00055. eCollection 2016.
Gastrointestinal (GI) cancer is the most common group of malignancies and many of its types are among the most deadly. Various glycoconjugates have been used in clinical practice as serum biomarker for several GI tumors, however, with limited diagnose application. Despite the good accessibility by endoscopy of many GI organs, the lack of reliable serum biomarkers often leads to late diagnosis of malignancy and consequently low 5-year survival rates. Recent advances in analytical techniques have provided novel glycoproteomic and glycomic data and generated functional information and putative biomarker targets in oncology. Glycosylation alterations have been demonstrated in a series of glycoconjugates (glycoproteins, proteoglycans, and glycosphingolipids) that are involved in cancer cell adhesion, signaling, invasion, and metastasis formation. In this review, we present an overview on the major glycosylation alterations in GI cancer and the current serological biomarkers used in the clinical oncology setting. We further describe recent glycomic studies in GI cancer, namely gastric, colorectal, and pancreatic cancer. Moreover, we discuss the role of glycosylation as a modulator of the function of several key players in cancer cell biology. Finally, we address several state-of-the-art techniques currently applied in this field, such as glycomic and glycoproteomic analyses, the application of glycoengineered cell line models, microarray and proximity ligation assay, and imaging mass spectrometry, and provide an outlook to future perspectives and clinical applications.
胃肠道（GI）癌是最常见的恶性肿瘤类型，其中许多类型是最致命的。多种糖缀合物已在临床实践中用作多种胃肠道肿瘤的血清生物标志物，然而，其诊断应用有限。尽管通过内窥镜检查可很好地观察许多胃肠道器官，但缺乏可靠的血清生物标志物常常导致恶性肿瘤的晚期诊断，从而导致5年生存率较低。分析技术的最新进展提供了新的糖蛋白质组学和糖组学数据，并在肿瘤学中生成了功能信息和假定的生物标志物靶点。在一系列参与癌细胞黏附、信号传导、侵袭和转移形成的糖缀合物（糖蛋白、蛋白聚糖和糖鞘脂）中已证实存在糖基化改变。在本综述中，我们概述了胃肠道癌中的主要糖基化改变以及临床肿瘤学中使用的当前血清生物标志物。我们进一步描述了胃肠道癌（即胃癌、结直肠癌和胰腺癌）中最近的糖组学研究。此外，我们讨论了糖基化作为癌细胞生物学中几个关键参与者功能调节剂的作用。最后，我们介绍了目前应用于该领域的几种先进技术，如糖组学和糖蛋白质组学分析、糖工程细胞系模型的应用、微阵列和邻近连接分析以及成像质谱，并展望了未来的前景和临床应用。
