Phosphatidylserine-positive extracellular vesicles for detecting multiple operable cancers
Early cancer detection is critical for reducing mortality. Circulating extracellular vesicles (EVs) offer diagnostic potential, yet reliable tumor-specific biomarkers and detection methods remain elusive. Using lipidomics analysis of EVs from eight cancer and five non-tumorigenic cell lines, we identified phosphatidylserine (PS) as a tumor-specific EV marker. PS-positive EVs were associated with apoptosis induction and tumor burden in both cellular and murine models. We developed PSEV-MultiCancer, a flow cytometry-based blood test detecting PS-positive EVs, achieving an area under the curve (AUC) of 0.932 (95% CI: 0.92-0.94) and a positive detection rate of 84.7% across 12 cancer types in a cohort of 1,869 clinical samples (including 1,269 cancer patients). Sensitivity for early-stage (I-II) cancers reached 74.7% with a specificity of 89.8%. Validation across three independent cohorts yielded AUC values of 0.97, 0.99, and 0.89, respectively. These findings support PSEV-MultiCancer as a promising noninvasive tool for early cancer detection, facilitating timely curative interventions.
Authors
- Shuo Zhang (ORCID: https://orcid.org/0009-0003-2798-0272)
- Gaoli Liang (ORCID: https://orcid.org/0000-0001-7252-0871)
- Ping Yang (ORCID: https://orcid.org/0000-0003-1689-6588)
- Yanbo Wang (ORCID: https://orcid.org/0000-0003-4052-6421)
- Shanting Gao
- Chiyuan Ma (ORCID: https://orcid.org/0000-0002-1710-5955)
- Yang Zhou (ORCID: https://orcid.org/0000-0001-8630-3464)
- Liuqing Yang (ORCID: https://orcid.org/0000-0002-6518-474X)
- Shoubin Zhan (ORCID: https://orcid.org/0000-0002-4528-9579)
- Xiyi Wei
- Peng R. Chen (ORCID: https://orcid.org/0000-0002-0402-7417)
- Xiaomin Bu
- Yize Li (ORCID: https://orcid.org/0009-0002-1919-3773)
- Xiao Li (ORCID: https://orcid.org/0000-0001-7866-3160)
- Xiangdong Li (ORCID: https://orcid.org/0000-0002-4044-2888)
- Zhibo Li (ORCID: https://orcid.org/0000-0002-9907-5533)
- Rui Xu (ORCID: https://orcid.org/0000-0003-4302-6393)
- Liwen Li (ORCID: https://orcid.org/0000-0003-3726-5013)
- Yiyuan Han
- Xiaoju Zhu (ORCID: https://orcid.org/0000-0002-8055-1544)
- Fangfang Jin (ORCID: https://orcid.org/0000-0002-8983-2529)
- Shengkai Zhou (ORCID: https://orcid.org/0009-0004-2338-8076)
Institutions
- James S. McDonnell Foundation (US)
- Nanjing University of Chinese Medicine (CN)
- Washington University in St. Louis (US)
- Zhejiang Cancer Hospital (CN)
- Jiangsu Cancer Hospital (CN)
- Nanjing University of the Arts (CN)
- Jiangsu Province Hospital (CN)
- Nanjing Medical University (CN)
- Nanjing University (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-09-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116259
- Citations
- 2
- Primary Topic
- Extracellular vesicles in disease
- Type
- article
- Field-Weighted Citation Impact
- 1.61
Funders
- National Natural Science Foundation of China
- Government of Jiangsu Province
- Natural Science Foundation of Jiangsu Province
- Nanjing University of Chinese Medicine
- Nanjing University
- Qinglan Project of Jiangsu Province of China
- Major Research Plan