Improved early detection of ovarian cancer using longitudinal multimarker models

Harry J. Whitwell, Jenny Worthington, Oleg Blyuss, Aleksandra Gentry-Maharaj, Andy Ryan, Richard Gunu, Jatinderpal Kalsi, Usha Menon, Ian Jacobs, Alexey Zaikin, John F. Timms

    Research output: Contribution to journalArticlepeer-review

    17 Citations (Scopus)
    26 Downloads (Pure)

    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.
    Original languageEnglish
    Pages (from-to)847-856
    Number of pages10
    JournalBritish Journal of Cancer (BJC)
    Volume122
    Issue number6
    Early online date15 Jan 2020
    DOIs
    Publication statusPublished - 17 Mar 2020

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