A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer
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Department of Obstetrics and Gynecology, Turku University Hospital and University of Turku, 20521 Turku, Finland
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Department of Gynecology, Charité—Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt Universität zu Berlin, and Berlin Institute of Health, Campus Virchow Klinikum, 13353 Berlin, Germany
3
Zora Biosciences Oy, 02150 Espoo, Finland
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Satasairaala Central Hospital, Department of Obstetrics and Gynecology, 28500 Pori, Finland
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Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany
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Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany
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Institute of Biomedicine and FICAN West Cancer Centre Cancer Research Unit, University of Turku, 20521 Turku, Finland
8
Department of Pathology and Research Program in Systems Oncology, University of Helsinki and Helsinki University Hospital, 00014 Helsinki, Finland
*
Author to whom correspondence should be addressed.
Academic Editor: Fabrizio Bianchi
Cancers 2021, 13(8), 1764; https://doi.org/10.3390/cancers13081764
Received: 23 February 2021
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Revised: 30 March 2021
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Accepted: 3 April 2021
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Published: 7 April 2021
(This article belongs to the Special Issue Cancer Biomarkers in Body Fluids)
Simple Summary
Most ovarian cancer patients initially show a response to primary treatments, but the development of refractory disease is a major problem. Currently, there are no blood-based prognostic biomarkers, and the prognosis of a patient is determined by the International Federation of Gynecology and Obstetrics (FIGO) stage and residual disease after cytoreductive surgery. In this study, we developed and validated a novel test based on the ratio of two circulatory lipids that enables the prognostic stratification of ovarian cancer patients at the time of diagnosis, prior to any oncological treatments. The translational relevance of this test is to find those patients with poor prognosis early on, and to identify patients that are at high risk of recurrence despite complete cytoreduction. Thus, the test enables the early direction of novel targeted therapies to those ovarian cancer patients at greatest risk of recurrence and death.
Epithelial ovarian cancer (EOC) generally responds well to oncological treatments, but the eventual development of a refractory disease is a major clinical problem. Presently, there are no prognostic blood-based biomarkers for the stratification of EOC patients at the time of diagnosis. We set out to assess and validate the prognostic utility of a novel two-lipid signature, as the lipidome is known to be markedly aberrant in EOC patients. The study consisted of 499 women with histologically confirmed EOC that were prospectively recruited at the university hospitals in Turku (Finland) and Charité (Berlin, Germany). Lipidomic screening by tandem liquid chromatography–mass spectrometry (LC-MS/MS) was performed for all baseline serum samples of these patients, and additionally for 20 patients of the Turku cohort at various timepoints. A two-lipid signature, based on the ratio of the ceramide Cer(d18:1/18:0) and phosphatidylcholine PC(O-38:4), showed consistent prognostic performance in all investigated study cohorts. In the Turku cohort, the unadjusted hazard ratios (HRs) per standard deviation (SD) (95% confidence interval) were 1.79 (1.40, 2.29) for overall and 1.40 (1.14, 1.71) for progression-free survival. In a Charité cohort incorporating only stage III completely resected patients, the corresponding HRs were 1.59 (1.08, 2.35) and 1.53 (1.02, 2.30). In linear-mixed models predicting progression of the disease, the two-lipid signature showed higher performance (beta per SD increase 1.99 (1.38, 2.97)) than cancer antigen 125 (CA-125, 1.78 (1.13, 2.87)). The two-lipid signature was able to identify EOC patients with an especially poor prognosis at the time of diagnosis, and also showed promise for the detection of disease relapse.
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Keywords:
ovarian cancer; lipidomics; lipid; prognosis; ceramide; phospholipid; plasmalogen; biomarker; patient stratification; outcome; personalized medicine
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MDPI and ACS Style
Salminen, L.; Braicu, E.I.; Lääperi, M.; Jylhä, A.; Oksa, S.; Hietanen, S.; Sehouli, J.; Kulbe, H.; Bois, A.d.; Mahner, S.; Harter, P.; Carpén, O.; Huhtinen, K.; Hynninen, J.; Hilvo, M. A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer. Cancers 2021, 13, 1764. https://doi.org/10.3390/cancers13081764
AMA Style
Salminen L, Braicu EI, Lääperi M, Jylhä A, Oksa S, Hietanen S, Sehouli J, Kulbe H, Bois Ad, Mahner S, Harter P, Carpén O, Huhtinen K, Hynninen J, Hilvo M. A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer. Cancers. 2021; 13(8):1764. https://doi.org/10.3390/cancers13081764
Chicago/Turabian StyleSalminen, Liina, Elena I. Braicu, Mitja Lääperi, Antti Jylhä, Sinikka Oksa, Sakari Hietanen, Jalid Sehouli, Hagen Kulbe, Andreas d. Bois, Sven Mahner, Philipp Harter, Olli Carpén, Kaisa Huhtinen, Johanna Hynninen, and Mika Hilvo. 2021. "A Novel Two-Lipid Signature Is a Strong and Independent Prognostic Factor in Ovarian Cancer" Cancers 13, no. 8: 1764. https://doi.org/10.3390/cancers13081764
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