Phosphatidylserine-positive extracellular vesicles for detecting multiple operable cancers
Fangfang Jin, Ping Yang, Rui Xu, Shuo Zhang, Liwen Li, Liuqing Yang, Xiaomin Bu, Shanting Gao, Yiyuan Han, Chiyuan Ma, Peng R. Chen, Zhibo Li, Shoubin Zhan, Gaoli Liang, Xiaoju Zhu, Shengkai Zhou, Xiangdong Li, Yize Li, Yang Zhou, Xiao Li, Xiyi Wei, Yanbo Wang
Abstract
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.