Tumour extracellular vesicle surface Protein-mRNA integration assay for early detection of epithelial ovarian cancerResearch in context

Tumour extracellular vesicle surface Protein-mRNA integration assay for early detection of epithelial ovarian cancerResearch in context

Summary: 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 promisin...

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Main Authors: Ying-Tzu Yen, Chen Zhao, Tian Gao, Jacqueline Ziqian Yang, Ning Kang, Jiahui Pu, Lei Qiu, Qixin Hu, Hyoyong Kim, Anmin Wang, Junseok Lee, Ryan Y. Zhang, Na Liu, Yue Ma, You-Ren Ji, Yong Ju, Lynn L. Zheng, James Lee-South, Vivian X. Zuo, Audrey Qian, Aaron Kwan, Yating Zhang, Shenghua Zhang, Zhili Wang, Jing Ren, Huaichao Liu, Zihan Wang, Yang Yue, Jina Kim, Jennifer Sun, Gabriella A. DiBernardo, Laura B. James-Allan, Ying Chen, Weipei Zhu, Guoyun Wang, Renjun Pei, Sanaz Memarzadeh, Sungyong You, Bobbie J. Rimel, Kate Lawrenson, Beth Y. Karlan, Myung Shin Sim, Shaohua Lu, Jipeng Wan, Na Sun, Hsian-Rong Tseng, Yazhen Zhu
Format: Article
Language:English
Published: Elsevier 2025-09-01
Series:EBioMedicine
Subjects:
Epithelial ovarian cancer
Extracellular vesicle
Liquid biopsy
Biomarker
Online Access:http://www.sciencedirect.com/science/article/pii/S2352396425003287
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Summary:Summary: 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, AUROC = 0.93, 95% CI: 0.88–0.98) and the subgroup of high-grade serous carcinoma (AUROC = 0.97, 95% CI: 0.87–0.97). Interpretation: The EOC EV SPRI assay demonstrated significant potential for early detection of EOC and improving long-term patient outcomes. Funding: This work is supported by National Institutes of Health (R01CA277530, R01CA255727, R01CA253651, R01CA253651-04S1, R21CA280444, R01CA246304, U01EB026421, R44CA288163, U01CA271887, and U01CA230705), DOD (HT9425-23-1-0361) and OCRA (CRDG-2023-3-1000) for the U.S. study. Additionally, we acknowledge the support of the Science and Technology Foundation of Suzhou (SZS2023006, SSD2023004) and the Youth Innovation Promotion Association CAS (2023335) for the work conducted at SINANO.
ISSN:2352-3964

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