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

IF 10.8 1区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

EBioMedicine Pub Date : 2025-09-01 Epub Date: 2025-08-12 DOI:10.1016/j.ebiom.2025.105884

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

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引用次数: 0

Abstract

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.

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肿瘤细胞外囊泡表面蛋白- mrna整合试验在上皮性卵巢癌早期检测中的应用。

背景：早期发现上皮性卵巢癌（EOC）对改善临床结果至关重要。然而，原发性血清学标志物癌抗原125 （CA125）检测早期EOC的敏感性不是最佳的。肿瘤来源的细胞外囊泡（EVs）是早期癌症检测的有前途的生物标志物。方法：建立EOC EV表面蛋白- mrna整合（SPRI）试验，早期检测EOC。该分析定量了由EV Click Beads富集的EOC EV亚群中的参考mrna，这些亚群针对三种EOC EV表面蛋白标记物。通过使用多组学数据的生物信息学框架选择三个EOC EV表面蛋白标记（即FRα， MSLN和TROP2），并使用EOC细胞系和EOC组织微阵列进行严格验证。然后，我们通过一项II期病例对照研究探索了EOC EV SPRI检测的转化潜力。在训练队列（n = 118）中采用逻辑回归模型建立EOC EV SPRI评分，然后在独立验证队列（n = 118）中进行验证。结果：EOC EV SPRI评分在区分良性卵巢肿块和健康供者方面表现优异，训练组和验证组的AUROC分别为0.99 （95% CI: 0.97-1.00）和0.93 （95% CI: 0.88-0.97）。它优于匹配的血清CA125，在早期EOC （I/II期，AUROC = 0.93, 95% CI: 0.88-0.98）和高级别浆液性癌亚组（AUROC = 0.97, 95% CI: 0.87-0.97）中仍然表现优异。解释：EOC EV SPRI检测显示出EOC早期检测和改善患者长期预后的巨大潜力。本研究由美国国立卫生研究院（R01CA277530, R01CA255727, R01CA253651, R01CA253651- 04s1, R21CA280444, R01CA246304, U01EB026421, R44CA288163, U01CA271887，和U01CA230705），美国国防部（HT9425-23-1-0361）和OCRA （crgd -2023-3-1000）支持。此外，我们还感谢苏州市科技基金（SZS2023006, SSD2023004）和中国科学院青年创新促进会（2023335）对在SINANO进行的工作的支持。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

EBioMedicine Biochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology

CiteScore

17.70

自引率

0.90%

发文量

579

审稿时长

5 weeks

期刊介绍： eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.