Medical University of South Carolina, Charleston, SC, United States.
Washington University School of Medicine in Saint Louis, St. Louis, MO, United States.
Adv Cancer Res. 2024;161:1-30. doi: 10.1016/bs.acr.2024.04.005. Epub 2024 Apr 25.
An overview of the role of glycosylation in prostate cancer (PCa) development and progression is presented, focusing on recent advancements in defining the N-glycome through glycomic profiling and glycoproteomic methodologies. Glycosylation is a common post-translational modification typified by oligosaccharides attached N-linked to asparagine or O-linked to serine or threonine on carrier proteins. These attached sugars have crucial roles in protein folding and cellular recognition processes, such that altered glycosylation is a hallmark of cancer pathogenesis and progression. In the past decade, advancements in N-glycan profiling workflows using Matrix Assisted Laser Desorption/Ionization Mass Spectrometry Imaging (MALDI-MSI) technology have been applied to define the spatial distribution of glycans in PCa tissues. Multiple studies applying N-glycan MALDI-MSI to pathology-defined PCa tissues have identified significant alterations in N-glycan profiles associated with PCa progression. N-glycan compositions progressively increase in number, and structural complexity due to increased fucosylation and sialylation. Additionally, significant progress has been made in defining the glycan and glycopeptide compositions of prostatic-derived glycoproteins like prostate-specific antigen in tissues and biofluids. The glycosyltransferases involved in these changes are potential drug targets for PCa, and new approaches in this area are summarized. These advancements will be discussed in the context of the further development of clinical diagnostics and therapeutics targeting glycans and glycoproteins associated with PCa progression. Integration of large scale spatial glycomic data for PCa with other spatial-omic methodologies is now feasible at the tissue and single-cell levels.
本文概述了糖基化在前列腺癌 (PCa) 发生和发展中的作用，重点介绍了通过糖组学分析和糖蛋白质组学方法定义 N-聚糖组的最新进展。糖基化是一种常见的翻译后修饰，其特点是寡糖通过 N-连接与天冬酰胺或 O-连接与丝氨酸或苏氨酸连接到载体蛋白上。这些连接的糖在蛋白质折叠和细胞识别过程中起着至关重要的作用，因此，糖基化的改变是癌症发病机制和进展的标志。在过去的十年中，使用基质辅助激光解吸/电离质谱成像 (MALDI-MSI) 技术的 N-糖链分析工作流程的进展已应用于定义 PCa 组织中聚糖的空间分布。多项应用 N-糖 MALDI-MSI 对病理学定义的 PCa 组织的研究已经确定了与 PCa 进展相关的 N-聚糖谱的显著改变。由于岩藻糖基化和唾液酸化的增加，N-聚糖的组成数量和结构复杂性逐渐增加。此外，在定义组织和生物流体中前列腺特异性抗原等前列腺衍生糖蛋白的聚糖和糖肽组成方面也取得了重大进展。参与这些变化的糖基转移酶是 PCa 的潜在药物靶点，该领域的新方法也得到了总结。这些进展将在针对与 PCa 进展相关的聚糖和糖蛋白的临床诊断和治疗的进一步发展的背景下进行讨论。现在可以在组织和单细胞水平上实现对 PCa 的大规模空间糖组学数据与其他空间组学方法的整合。
