A metabolite-based liquid biopsy for detection of ovarian cancer

作者：Johannes F. Fahrmann, Seyyed Mahmood Ghasemi, Chae Young Han, Ranran Wu, Jennifer B. Dennison, Jody V. Vykoukal, Joseph Celestino, Karen Lu, Zhen Lü, Charles W. Drescher, Kim‐Anh Do, Samir Hanash, Robert C. Bast, Ehsan Irajizad · 发表于：Biomarker Research · 年份：2024 · DOI：10.1186/s40364-024-00629-2 · 被引用次数：8 · 研究领域：Ovarian cancer diagnosis and treatment、Endometrial and Cervical Cancer Treatments、Intraperitoneal and Appendiceal Malignancies

Serial CA125 and second line transvaginal ultrasound (TVS) screening in the UKCTOCS indicated a shift towards detection of earlier stage ovarian cancer (OvCa), but did not yield a significant mortality reduction. There remains a need to establish additional biomarkers that can complement CA125 for even earlier and at a larger proportion of new cases. Using a cohort of plasma samples from 219 OvCa cases (59 stage I/II and 160 stage III/IV) and 409 female controls and a novel Sensitivity Maximization At A Given Specificity (SMAGS) method, we developed a blood-based metabolite-based test consisting of 7 metabolites together with CA125 for detection of OvCa. At a 98.5% specificity cutpoint, the metabolite test achieved sensitivity of 86.2% for detection of early-stage OvCa and was able to capture 64% of the cases with low CA125 levels (< 35 units/mL). In an independent test consisting of 65 early-stage OvCa cases and 141 female controls, the metabolite panel achieved sensitivity of 73.8% at a 91.4% specificity and captured 13 (44.8%) out of 29 early-stage cases with CA125 levels < 35 units/mL. The metabolite test has utility for ovarian cancer screening, capable of improving upon CA125 for detection of early-stage disease.