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  • Gentry-Maharaj, Aleksandra  (2)
  • Menon, Usha  (2)
  • 1
    In: Communications Medicine, Springer Science and Business Media LLC, Vol. 3, No. 1 ( 2023-01-20)
    Abstract: Earlier detection of pancreatic ductal adenocarcinoma (PDAC) is key to improving patient outcomes, as it is mostly detected at advanced stages which are associated with poor survival. Developing non-invasive blood tests for early detection would be an important breakthrough. Methods The primary objective of the work presented here is to use a dataset that is prospectively collected, to quantify a set of cancer-associated proteins and construct multi-marker models with the capacity to predict PDAC years before diagnosis. The data used is part of a nested case-control study within the UK Collaborative Trial of Ovarian Cancer Screening and is comprised of 218 samples, collected from a total of 143 post-menopausal women who were diagnosed with pancreatic cancer within 70 months after sample collection, and 249 matched non-cancer controls. We develop a stacked ensemble modelling technique to achieve robustness in predictions and, therefore, improve performance in newly collected datasets. Results Here we show that with ensemble learning we can predict PDAC status with an AUC of 0.91 (95% CI 0.75–1.0), sensitivity of 92% (95% CI 0.54–1.0) at 90% specificity, up to 1 year prior to diagnosis, and at an AUC of 0.85 (95% CI 0.74–0.93) up to 2 years prior to diagnosis (sensitivity of 61%, 95% CI 0.17–0.83, at 90% specificity). Conclusions The ensemble modelling strategy explored here outperforms considerably biomarker combinations cited in the literature. Further developments in the selection of classifiers balancing performance and heterogeneity should further enhance the predictive capacity of the method.
    Type of Medium: Online Resource
    ISSN: 2730-664X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 3096949-9
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  • 2
    In: British Journal of Cancer, Springer Science and Business Media LLC, Vol. 122, No. 6 ( 2020-03-17), p. 847-856
    Abstract: 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.
    Type of Medium: Online Resource
    ISSN: 0007-0920 , 1532-1827
    RVK:
    RVK:
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2002452-6
    detail.hit.zdb_id: 80075-2
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