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Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden

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Abstract

Evaluation of protein and metabolite expression patterns in blood using mass spectrometry and high-throughput antibody-based screening platforms has potential for the discovery of new biomarkers for managing breast cancer patient treatment. Previously identified blood-based breast cancer biomarkers, including cancer antigen 15.3 (CA15-3) are useful in combination with imaging (computed tomography scans, magnetic resonance imaging, X-rays) and physical examination for monitoring tumour burden in advanced breast cancer patients. However, these biomarkers suffer from insufficient levels of accuracy and with new therapies available for the treatment of breast cancer, there is an urgent need for reliable, non-invasive biomarkers that measure tumour burden with high sensitivity and specificity so as to provide early warning of the need to switch to an alternative treatment. The aim of this study was to identify a biomarker signature of tumour burden using cancer and non-cancer (healthy controls/non-malignant breast disease) patient samples. Results demonstrate that combinations of three candidate biomarkers from Glutamate, 12-Hydroxyeicosatetraenoic acid, Beta-hydroxybutyrate, Factor V and Matrix metalloproteinase-1 with CA15-3, an established biomarker for breast cancer, were found to mirror tumour burden, with AUC values ranging from 0.71 to 0.98 when comparing non-malignant breast disease to the different stages of breast cancer. Further validation of these biomarker panels could potentially facilitate the management of breast cancer patients, especially to assess changes in tumour burden in combination with imaging and physical examination.

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Acknowledgments

The All-Ireland Cooperative Oncology Research Group (ICORG) assisted in the provision of clinical samples. This work was supported by funding from Enterprise Ireland (EI) [Grant number CF20122012].

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Authors and Affiliations

  1. Department of Biology, The National University of Ireland Maynooth, Maynooth, Kildare, Ireland

    Paul Dowling

  2. National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

    Paul Dowling, Michael Henry, Paula Meleady, Colin Clarke, Vincent Lynch, Michael Moriarty & Martin Clynes

  3. Institute of Molecular Medicine, Trinity Centre for Health Sciences, Trinity College Dublin, St. James’ Hospital, Dublin, Ireland

    Kathy Gately & Kenneth O’Byrne

  4. Department of Surgery, St. James’s Hospital, Dublin, Ireland

    Elizabeth Connolly

  5. Molecular Therapeutics for Cancer Ireland (MTCI), St. Vincent’s University Hospital, Dublin, Ireland

    Jo Ballot, Giuseppe Gullo & John Crown

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  1. Paul Dowling
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  3. Paula Meleady
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Correspondence to Paul Dowling.

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Paul Dowling and Michael Henry are joint authors.

Michael Moriarty and Martin Clynes are joint authors.

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Dowling, P., Henry, M., Meleady, P. et al. Metabolomic and proteomic analysis of breast cancer patient samples suggests that glutamate and 12-HETE in combination with CA15-3 may be useful biomarkers reflecting tumour burden. Metabolomics 11, 620–635 (2015). https://doi.org/10.1007/s11306-014-0723-1

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