High-grade ovarian serous carcinoma patients exhibit profound alterations in lipid metabolism

Abstract

// Elena Ioana Braicu 1, 2 , Silvia Darb-Esfahani 3, 2 , Wolfgang D. Schmitt 3 , Kaisa M. Koistinen 4 , Laura Heiskanen 4 , Päivi Pöhö 5, 6 , Jan Budczies 3 , Marc Kuhberg 1 , Manfred Dietel 3 , Christian Frezza 7 , Carsten Denkert 3 , Jalid Sehouli 1, 2 and Mika Hilvo 4, 5 1 Department of Gynecology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany 2 On Behalf of the Tumor Bank Ovarian Cancer Network, Berlin, Germany 3 Institute of Pathology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Tumor bank Ovarian Cancer Network, Berlin, Germany 4 Zora Biosciences Oy, Espoo, Finland 5 VTT Technical Research Centre of Finland, Espoo, Finland 6 Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland 7 MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK Correspondence to: Mika Hilvo, email: mika.hilvo@zora.fi Keywords: lipidomics; biomarker; diagnosis; prognosis; ovarian cancer Received: June 14, 2016      Accepted: October 11, 2017      Published: October 26, 2017 ABSTRACT Ovarian cancer is a very severe type of disease with poor prognosis. Treatment of ovarian cancer is challenging because of the lack of tests for early detection and effective therapeutic targets. Thus, new biomarkers are needed for both diagnostics and better understanding of the cellular processes of the disease. Small molecules, consisting of metabolites or lipids, have shown emerging potential for ovarian cancer diagnostics. Here we performed comprehensive lipidomic profiling of serum and tumor tissue samples from high-grade serous ovarian cancer patients to find lipids that were altered due to cancer and also associated with progression of the disease. Ovarian cancer patients exhibited an overall reduction of most lipid classes in their serum as compared to a control group. Despite the overall reduction, there were also specific lipids showing elevation, and especially alterations in ceramide and triacylglycerol lipid species were dependent on their fatty acyl side chain composition. Several lipids showed progressive alterations in patients with more advanced disease and poorer overall survival, and outperformed CA-125 as prognostic markers. The abundance of many serum lipids correlated with their abundance in tumor tissue samples. Furthermore, we found a negative correlation of serum lipids with 3-hydroxybutyric acid, suggesting an association between decreased lipid levels and fatty acid oxidation. In conclusion, here we present a comprehensive analysis of lipid metabolism alterations in ovarian cancer patients, with clinical implications.