Multi-analyte approach combining cfDNA sequencing and protein testing for early ovarian cancer detection
Non-invasive liquid biopsy is a promising strategy for ovarian cancer (OC) detection. We evaluated the feasibility and efficacy of a multi-analyte approach combining circulating tumor DNA (ctDNA) detection with protein biomarkers for early OC detection. At 95% specificity, CA125 and ctDNA alone exhibited an overall sensitivity of 79.0% and 58.7%, respectively; however, when CA125 was combined with ctDNA, sensitivity reached 85.5%. Integrating CA125 and human epididymis protein-4 (HE4) in the risk of ovarian malignancy algorithm (ROMA) index, yielded a sensitivity of 86.2%. When four additional proteins (HE4, cancer antigen 19-9, prolactin, and interleukin-6) were added to CA125 and ctDNA in the EarlySEEK model, sensitivity increased to 94.2%. Meanwhile, the EarlySEEK model was not affected by menopausal status, and outperformed CA125 in distinguishing benign and malignant ovarian tumors. These findings demonstrate that EarlySEEK could effectively identify OC at early stage when they are more likely to be curable.
Authors
- Siqi Yang (ORCID: https://orcid.org/0009-0003-1779-2411)
- Zhuoqun Lin (ORCID: https://orcid.org/0009-0004-2177-5064)
- Fenfen Wang (ORCID: https://orcid.org/0000-0003-1095-8127)
- Lingjia Lu
- Xiaodong Cheng (ORCID: https://orcid.org/0000-0002-6073-7261)
- Tao Zhu (ORCID: https://orcid.org/0000-0002-2921-4067)
- Lingfang Wang (ORCID: https://orcid.org/0000-0002-9002-3657)
- Lingjun Zhao
- Xiaojing Chen
- Yang Li (ORCID: https://orcid.org/0000-0002-0752-6166)
- Zhuyan Shao
- Jie Dong (ORCID: https://orcid.org/0000-0002-8148-3838)
- Fangfang Qian (ORCID: https://orcid.org/0000-0001-6628-9183)
- Ziyu Xing
- Senmi Qian
Institutions
- Chinese Academy of Sciences (CN)
- Zhejiang Cancer Hospital (CN)
- Third People's Hospital of Hangzhou (CN)
- Women's Hospital, School of Medicine, Zhejiang University (CN)
- Huzhou Women and Children's Hospital (CN)
- Hangzhou Cancer Hospital (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-05-09
- DOI
- https://doi.org/10.1016/j.isci.2025.112617
- Citations
- 2
- Primary Topic
- Cancer Genomics and Diagnostics
- Type
- article
- Field-Weighted Citation Impact
- 1.87
Funders
- National Natural Science Foundation of China
- National Key Research and Development Program of China
- Fundamental Research Funds for the Central Universities
- Science and Technology Department of Zhejiang Province
- Science and Technology Program of Zhejiang Province