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. 2024 Aug 28;12(1):91.
doi: 10.1186/s40364-024-00629-2.

A metabolite-based liquid biopsy for detection of ovarian cancer

Johannes F Fahrmann  1 , Seyyed Mahmood Ghasemi  2 , Chae Y Han  3 , Ranran Wu  1 , Jennifer B Dennison  1 , Jody Vykoukal  1 , Joseph Celestino  4 , Karen Lu  3 , Zhen Lu  3 , Charles Drescher  5   6 , Kim-Anh Do  2 , Samir Hanash  1 , Robert C Bast  3 , Ehsan Irajizad  7
Affiliations

A metabolite-based liquid biopsy for detection of ovarian cancer

Johannes F Fahrmann et al. Biomark Res. .

Abstract

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.

Keywords: Biomarkers; Early detection; Metabolites; Ovarian cancer.

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Conflict of interest statement

Dr. Bast receives royalties from Fujirebio Diagnostics, Inc, for the discovery of CA125.

Figures

Fig. 1
Fig. 1
Performance estimates of the SMAGS model for detection of early-stage ovarian cancer in the EDRN Reference Set. A AUC curves for the SMAGS model and CA125 for detection of early-stage ovarian cancer. B AUC curves for the SMAGS model for detection of early-stage ovarian cancer among individuals with CA125 levels < 35 units/mL
Fig. 2
Fig. 2
Performance estimates of the SMAGs model for detection of early-stage ovarian cancer in the independent Test Set. A AUC curves for the SMAGs model and CA125 for detection of early-stage ovarian cancer. B AUC curves for the SMAGs model for detection of early-stage ovarian cancer among individuals with CA125 levels < 35 units/mL
See this image and copyright information in PMC

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