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        Improved early detection of ovarian cancer using longitudinal multimarker models

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        s41416_019_0718_9.pdf (PDF, 1Mb)
        Author
        Whitwell, Harry J.
        Worthington, Jenny
        Blyuss, Oleg
        Gentry-Maharaj, Aleksandra
        Ryan, Andy
        Gunu, Richard
        Kalsi, Jatinderpal
        Menon, Usha
        Jacobs, Ian
        Zaikin, Alexey
        Timms, John F.
        Attention
        2299/22167
        Abstract
        Background: Ovarian cancer has a poor survival rate due to late diagnosis and improved methods are needed for its early detection. Our primary objective was to identify and incorporate additional biomarkers into longitudinal models to improve on the performance of CA125 as a first-line screening test for ovarian cancer. Methods: This case–control study nested within UKCTOCS used 490 serial serum samples from 49 women later diagnosed with ovarian cancer and 31 control women who were cancer-free. Proteomics-based biomarker discovery was carried out using pooled samples and selected candidates, including those from the literature, assayed in all serial samples. Multimarker longitudinal models were derived and tested against CA125 for early detection of ovarian cancer. Results: The best performing models, incorporating CA125, HE4, CHI3L1, PEBP4 and/or AGR2, provided 85.7% sensitivity at 95.4% specificity up to 1 year before diagnosis, significantly improving on CA125 alone. For Type II cases (mostly high-grade serous), models achieved 95.5% sensitivity at 95.4% specificity. Predictive values were elevated earlier than CA125, showing the potential of models to improve lead time. Conclusions: We have identified candidate biomarkers and tested longitudinal multimarker models that significantly improve on CA125 for early detection of ovarian cancer. These models now warrant independent validation.
        Publication date
        2020-03-17
        Published in
        British Journal of Cancer
        Published version
        https://doi.org/10.1038/s41416-019-0718-9
        Other links
        http://hdl.handle.net/2299/22167
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