近日，复旦大学张颖团队报道了化学糖蛋白组学方法解密尿细胞外囊泡表面体用于前列腺癌的诊断和分级。相关论文于2025年9月23日发表在《德国应用化学》杂志上。

细胞外囊泡（EV）表面蛋白是决定EV通讯功能的基本信号介质。EV表面蛋白质组（surfaceome）的选择性和深度探索是非常引人注目的，但由于表面蛋白质独特的物理化学性质，在技术上仍然具有挑战性。这些障碍由于EV固有的异质性和生物流体中表面目标的低丰度而进一步复杂化。

研究组开发了一种化学糖蛋白组学策略，EVscope （EV表面综合一锅蛋白质组学探索），以全面分析EV表面组。亲水和芳香亲脂基团修饰的磁珠可以实现无偏置EV分离和原位氧化，并在表面蛋白质上标记顺式二醇。随后的从头过程，包括EV裂解，蛋白质消化和表面糖肽富集，共同最大化表面小体覆盖。EVscope应用于368例前列腺相关疾病患者的尿液样本，鉴定出1121种EV表面蛋白，建立了迄今为止最大的尿源性EV表面体数据集，并鉴定出组织蛋白酶L、整合素α 3、纤维蛋白原β链和四蛋白-1作为特征蛋白，具有作为前列腺癌诊断和分级的无创生物标志物的潜力。总之，该研究建立了一种高分辨率EV表面体分析的创新方法，促进了无创生物标志物的发现，并实现了在人群规模筛选中的直接检测。

附：英文原文

Title: A Chemical Glycoproteomic Approach Decrypts Urinary Extracellular Vesicle Surfaceome for Prostate Cancer Diagnosis and Grading

Author: Yuhan Cai, Aixiang Bu, Shanying Han, Yajie Ding, Hao Zhang, Jie Sun, Yuanyuan Deng, Jingyuan Ma, Shangqian Wang, Yanhong Gu, Wenya Chang, Zhongze Gu, Zhuoying Xie, Lianghai Hu, Ying Zhang

Issue&Volume: 2025-09-23

Abstract: Extracellular vesicle (EV) surface proteins serve as the fundamental signaling mediators, determining the communication function of EVs. The selective and in-depth exploration of EV surface proteome (surfaceome) is highly compelling but remains technically challenging due to the unique physicochemical properties of surface proteins. These hurdles are further compounded by the inherent heterogeneity of EVs and the low abundance of surface targets in biofluids. Herein, we developed a chemical glycoproteomic strategy, EVscope (EV surface comprehensive one-pot proteomic exploration), for comprehensively profiling the EV surfaceome. The hydrophilic and aromatic lipophilic group-modified magnetic beads enable bias-free EV isolation and in situ oxidation and labeling of cis-diols on surface proteins. Subsequent on-bead processes, including EV lysis, protein digestion, and surface glycopeptide enrichment, collectively maximize surfaceome coverage. Applied to urine samples from 368 individuals with prostate-related diseases, EVscope identified 1,121 EV surface proteins, establishing the largest urine-derived EV surfaceome dataset to date and identifying cathepsin L, integrin alpha 3, fibrinogen beta chain, and tetraspanin-1 as characteristic proteins with potential as noninvasive biomarkers for prostate cancer diagnosis and grading. In summary, this study establishes an innovative methodology for high-resolution EV surfaceome analysis, facilitating noninvasive biomarker discovery and enabling direct detection in population-scale screening.

DOI: 10.1002/anie.202509399

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202509399