High-grade ovarian serous carcinoma patients exhibit profound alterations in lipid metabolism
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Elena Ioana Braicu1,2, Silvia Darb-Esfahani3,2, Wolfgang D. Schmitt3, Kaisa M. Koistinen4, Laura Heiskanen4, Päivi Pöhö5,6, Jan Budczies3, Marc Kuhberg1, Manfred Dietel3, Christian Frezza7, Carsten Denkert3, Jalid Sehouli1,2 and Mika Hilvo4,5
1Department of Gynecology, Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany
2On Behalf of the Tumor Bank Ovarian Cancer Network, Berlin, Germany
3Institute 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
4Zora Biosciences Oy, Espoo, Finland
5VTT Technical Research Centre of Finland, Espoo, Finland
6Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland
7MRC Cancer Unit, Hutchison/MRC Research Centre, University of Cambridge, Cambridge, UK
Mika Hilvo, email: [email protected]
Keywords: lipidomics; biomarker; diagnosis; prognosis; ovarian cancer
Received: June 14, 2016 Accepted: October 11, 2017 Published: October 26, 2017
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.
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