Cu isotope ratios are meaningful in ovarian cancer diagnosis
Benoît Toubhans, Alexandra T. Gourlan, Philippe Télouk, Kerryn Lutchman-Singh, Lewis W. Francis, R. Steven Conlan, Lavinia Margarit, Deyarina González, Laurent Charlet
Abstract
Ovarian cancer diagnosis is currently based on imaging and circulating CA-125 concentrations with well-known limits to sensitivity and specificity. New biomarkers are required to complement CA-125 testing to increase effectiveness. Increases in sensitivity of isotopic separation via multi collector inductively coupled plasma-mass spectrometry have recently allowed highly accurate measurement of copper (Cu) isotopic variations. Studies in breast cancer patients have revealed changes of serum copper isotopic composition demonstrating the potential for development as a cancer biomarker. Evaluating 65Cu/63Cu ratios (δ65Cu) in serum samples from cancer patients has revealed a strong correlation with cancer development. In this study blood samples from forty-four ovarian cancer patients, and 13 ovarian biopsies were investigated. Here we demonstrate that changes in Cu isotopes also occurs in ovarian cancer patients. Copper composition determined by multiple collector inductively coupled plasma mass spectrometry revealed that the copper isotopic ratio δ65Cu in the plasma of 44 ovarian cancer patient cohort was significantly lower than in a group of 48 healthy donors, and indicated that serum was enriched for 63Cu. Further analysis revealed that the isotopic composition of tumour biopsies was enriched for 65Cu compared with adjacent healthy ovarian tissues. We propose that these changes are due to increase lactate and Cu transporter activities in the tumour. These observations demonstrate that, combined with existing strategies, δ65Cu could be developed for use in ovarian cancer early detection.