Tumour extracellular vesicle surface Protein-mRNA integration assay for early detection of epithelial ovarian cancer

作者：Ying-Tzu Yen, Chen Zhao, Tian Gao, Jianwei Yang, Ning Kang, Jiahui Pu, Lei Qiu, Qixin Hu, Hyo Yong Kim, An Min Wang, Junseok Lee, Ryan Y. Zhang, Na Liu, Yue Ma, You‐Ren Ji, Yong Ju, Li Zheng, James Lee-South, Vivian Xufei Zuo, Audrey Qian, Aaron Kwan, Yating Zhang, Shenghua Zhang, Zhili Wang, Jing Ren, Huaichao Liu, Zihan Wang, Yue Yang, Jina Kim, Jennifer K. Sun, Gabriella DiBernardo, Laura B. James‐Allan, Ying Chen, Weipei Zhu, Guoyun Wang, Renjun Pei, Sanaz Memarzadeh, Sungyong You, B.J. Rimel, Kate Lawrenson, Beth Karlan, Myung‐Shin Sim, Shaohua Lu, Jipeng Wan, Na Sun, Hsian‐Rong Tseng, Yazhen Zhu · 发表于：EBioMedicine · 年份：2025 · DOI：10.1016/j.ebiom.2025.105884 · 被引用次数：6 · 研究领域：Extracellular vesicles in disease、interferon and immune responses、Ovarian cancer diagnosis and treatment

BACKGROUND: Early detection of epithelial ovarian cancer (EOC) is crucial for improving clinical outcomes. However, the sensitivity of primary serological marker cancer antigen 125 (CA125) is suboptimal for detecting early-stage EOC. Tumour-derived extracellular vesicles (EVs) are promising biomarkers for early cancer detection. METHODS: We developed an EOC EV Surface Protein-mRNA Integration (SPRI) Assay for early detection of EOC. This assay quantifies reference mRNAs within subpopulations of EOC EVs enriched by EV Click Beads targeting three EOC EV surface protein markers. Three EOC EV surface protein markers (i.e., FRα, MSLN, and TROP2) were selected through a bioinformatic framework using multi-omics data and underwent rigorous validation using EOC cell lines and EOC tissue microarrays. We then explored the translational potential of the EOC EV SPRI Assay through a phase II case-control study. The EOC EV SPRI Score was established using a logistic regression model in a training cohort (n = 118) and then validated in an independent validation cohort (n = 118). FINDINGS: EOC EV SPRI Score demonstrated superior performance for distinguishing EOC from benign ovarian masses and healthy donors with an area under the receiver operating characteristic (AUROC) of 0.99 (95% CI: 0.97-1.00) in the training cohort and 0.93 (95% CI: 0.88-0.97) in the validation cohort. It outperformed matched serum CA125, and the performance remained excellent in earlier stages of EOC (Stage I/II, AUR...