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Urinary extracellular vesicle N-glycomics identifies diagnostic glycosignatures for bladder cancer

Author

Listed:
  • Yang Li

    (Fudan University)

  • Bin Fu

    (Fudan University)

  • Maoyu Wang

    (Naval Medical University)

  • Weiyu Chen

    (Fudan University)

  • Jiawei Fan

    (Fudan University)

  • Yueyue Li

    (Fudan University)

  • Xuejiao Liu

    (Fudan University)

  • Jun Wang

    (Fudan University)

  • Zhensheng Zhang

    (Naval Medical University)

  • Haojie Lu

    (Fudan University
    Fudan University)

  • Ying Zhang

    (Fudan University
    Fudan University)

Abstract

Bladder cancer (BC) is the most common urologic malignancy, facing enormous diagnostic challenges. Urinary extracellular vesicles (EVs) are promising source for developing diagnostic markers for bladder cancer because of the direct contact between urine and bladder. This study pioneers urinary EV N-glycomics for bladder cancer diagnosis. We have generated a comprehensive N-glycome landscape of urinary EVs through high-throughput N-glycome analysis, identifying a total of 252 N-glycans from 333 individuals. In bladder cancer patients, urinary EVs exhibit decreased fucosylation and increased sialylation level. An Eight N-glycan diagnostic model demonstrates strong performance in both validation cohorts, achieving ROC AUC values of 0.88 and 0.86, respectively. Furthermore, this model successfully differentiates both non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) from healthy individuals, underscoring the model’s superiority. Moreover, urinary EVs N-glycoproteomic analysis reveals that the glycoproteins carrying cancer-associated N-glycan signatures are closely associated with immune activities. The N-glycome comparative analysis of EVs and their source cells indicate that the glycosylation profiles of EVs do not completely match the glycosylation backgrounds of their source cells. In summary, our study establishes urinary EV N-glycomics as a non-invasive BC screening tool and provide a framework for EV glycan biomarker discovery across cancers.

Suggested Citation

  • Yang Li & Bin Fu & Maoyu Wang & Weiyu Chen & Jiawei Fan & Yueyue Li & Xuejiao Liu & Jun Wang & Zhensheng Zhang & Haojie Lu & Ying Zhang, 2025. "Urinary extracellular vesicle N-glycomics identifies diagnostic glycosignatures for bladder cancer," Nature Communications, Nature, vol. 16(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-57633-9
    DOI: 10.1038/s41467-025-57633-9
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    References listed on IDEAS

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    1. Hyunku Shin & Byeong Hyeon Choi & On Shim & Jihee Kim & Yong Park & Suk Ki Cho & Hyun Koo Kim & Yeonho Choi, 2023. "Single test-based diagnosis of multiple cancer types using Exosome-SERS-AI for early stage cancers," Nature Communications, Nature, vol. 14(1), pages 1-10, December.
    2. Keyang Xu & Ai Fu & Zhaoyi Li & Liangbin Miao & Zhonghan Lou & Keying Jiang & Condon Lau & Tao Su & Tiejun Tong & Jianfeng Bao & Aiping Lyu & Hiu Yee Kwan, 2024. "Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    3. Ana Martinez-Val & Dorte B. Bekker-Jensen & Sophia Steigerwald & Claire Koenig & Ole Østergaard & Adi Mehta & Trung Tran & Krzysztof Sikorski & Estefanía Torres-Vega & Ewa Kwasniewicz & Sólveig Hlín B, 2021. "Spatial-proteomics reveals phospho-signaling dynamics at subcellular resolution," Nature Communications, Nature, vol. 12(1), pages 1-17, December.
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