Wang Fenfen, Wang Lingfang, Xing Ziyu, Lu Lingjia, Lin Zhuoqun, Qian Senmi, Zhu Tao, Shao Zhuyan, Zhao Lingjun, Dong Jie, Qian Fangfang, Li Yang, Chen Xiaojing, Yang Siqi, Cheng Xiaodong
Department of Gynecologic Oncology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, China.
Zhejiang Key Laboratory of Precision Diagnosis and Therapy for Major Gynecological Diseases, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.
iScience. 2025 May 8;28(6):112617. doi: 10.1016/j.isci.2025.112617. eCollection 2025 Jun 20.
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.
非侵入性液体活检是一种很有前景的卵巢癌（OC）检测策略。我们评估了一种多分析物方法的可行性和有效性，该方法将循环肿瘤DNA（ctDNA）检测与蛋白质生物标志物相结合用于早期OC检测。在特异性为95%时，单独的CA125和ctDNA的总体敏感性分别为79.0%和58.7%；然而，当CA125与ctDNA联合使用时，敏感性达到85.5%。将CA125和人附睾蛋白4（HE4）纳入卵巢恶性肿瘤风险算法（ROMA）指数中，敏感性为86.2%。在EarlySEEK模型中，当在CA125和ctDNA基础上再添加另外四种蛋白质（HE4、癌抗原19-9、催乳素和白细胞介素-6）时，敏感性提高到94.2%。同时，EarlySEEK模型不受绝经状态的影响，在区分卵巢良性和恶性肿瘤方面优于CA125。这些发现表明，EarlySEEK能够在早期OC更有可能治愈时有效地识别它们。
