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Metabolomic biomarkers for the detection of obesity-driven endometrial cancer
Njoku, K. Campbell, A. E. Geary, B. MacKintosh, M. L. Derbyshire, A. E. Kitson, S. J. Sivalingam, V. N. Pierce, Andrew Whetton, Anthony D Crosbie, E. J.
Njoku, K.
Campbell, A. E.
Geary, B.
MacKintosh, M. L.
Derbyshire, A. E.
Kitson, S. J.
Sivalingam, V. N.
Pierce, Andrew
Whetton, Anthony D
Crosbie, E. J.
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Abstract
Endometrial cancer is the most common malignancy of the female genital tract and a major cause of morbidity and mortality in women. Early detection is key to ensuring good outcomes but a lack of minimally invasive screening tools is a significant barrier. Most endometrial cancers are obesity-driven and develop in the context of severe metabolomic dysfunction. Blood-derived metabolites may therefore provide clinically relevant biomarkers for endometrial cancer detection. In this study, we analysed plasma samples of women with body mass index (BMI) ≥30kg/m2 and endometrioid endometrial cancer (cases, n = 67) or histologically normal endometrium (controls, n = 69), using a mass spectrometry-based metabolomics approach. Eighty percent of the samples were randomly selected to serve as a training set and the remaining 20% were used to qualify test performance. Robust predictive models (AUC > 0.9) for endometrial cancer detection based on artificial intelligence algorithms were developed and validated. Phospholipids were of significance as biomarkers of endometrial cancer, with sphingolipids (sphingomyelins) discriminatory in post-menopausal women. An algorithm combining the top ten performing metabolites showed 92.6% prediction accuracy (AUC of 0.95) for endometrial cancer detection. These results suggest that a simple blood test could enable the early detection of endometrial cancer and provide the basis for a minimally invasive screening tool for women with a BMI ≥ 30 kg/m2.
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Date
2021
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Article
Citation
Njoku K, Campbell AE, Geary B, MacKintosh ML, Derbyshire AE, Kitson SJ, et al. Metabolomic Biomarkers for the Detection of Obesity-Driven Endometrial Cancer. Cancers (Basel). 2021;13(4).