Untargeted lipidomics reveal association of elevated plasma C18 ceramide levels with reduced survival in metastatic castration-resistant prostate cancer patients.

Autor: Cattrini C; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132, Genoa, Italy. carlo.cattrini@gmail.com.; Medical Oncology, 'Maggiore Della Carità' University Hospital, 28100, Novara, Italy. carlo.cattrini@gmail.com., Manfredi M; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy.; Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale, 28100, Novara, Italy., Barboro P; UO Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico S. Martino, 16132, Genova, Italy., Ghirimoldi M; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy.; Center for Translational Research on Autoimmune and Allergic Diseases (CAAD), University of Piemonte Orientale, 28100, Novara, Italy., Mennitto A; Medical Oncology, 'Maggiore Della Carità' University Hospital, 28100, Novara, Italy.; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Martini V; Medical Oncology, 'Maggiore Della Carità' University Hospital, 28100, Novara, Italy., Battioni A; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Le Van M; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Gobbato S; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Branni C; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Ayed RB; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy., Pinato DJ; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy.; Department of Surgery and Cancer, Imperial College London, Hammersmith Hospital Campus, London, UK., Catalano F; UO Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico S. Martino, 16132, Genova, Italy., Zanardi E; UO Clinica Di Oncologia Medica, IRCCS Ospedale Policlinico S. Martino, 16132, Genova, Italy., Boccardo F; Department of Internal Medicine and Medical Specialties (DIMI), School of Medicine, University of Genoa, 16132, Genoa, Italy., Gennari A; Medical Oncology, 'Maggiore Della Carità' University Hospital, 28100, Novara, Italy.; Department of Translational Medicine, University of Piemonte Orientale (UPO), 28100, Novara, Italy.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Oct 18; Vol. 13 (1), pp. 17791. Date of Electronic Publication: 2023 Oct 18.
DOI: 10.1038/s41598-023-44157-9
Abstrakt: Emerging evidence highlights the potential prognostic relevance of circulating lipids in metastatic castration-resistant prostate cancer (mCRPC), with a proposed 3-lipid signature. This study aims to analyze the lipidomic profiles of individuals with mCRPC to identify lipid species that could serve as predictive indicators of prognosis and therapeutic response. Plasma samples were collected from mCRPC patients initiating first-line treatment (1 L) (n = 29) and those previously treated with at least two lines of therapy (> 2 L) (n = 19), including an androgen-receptor signaling inhibitor and a taxane. Employing an untargeted lipidomic approach, lipids were extracted from the plasma samples and subjected to analysis. A comprehensive identification and quantification of 789 plasma lipids was achieved. Notably, 75 species displayed significant dysregulation in > 2 L patients in comparison to the 1 L group. Among these, 63 species exhibited elevated levels, while 12 were reduced. Patients included in > 2 L cohort showed elevated levels of acylcarnitines (CAR), diacylglycerols (DG), phosphatidylethanolamines (PE), triacylglycerols (TG), and ceramides (Cer). Notably, some upregulated lipids, including CAR 14:0, CAR 24:1, Cer d18:1/16:0, Cer d18:1/18:0 (C18 Cer), Cer d18:2/18:0, Cer d18:1/24:1, and Cer d20:1/24:1, showed significant associations with overall survival (OS) in univariate models. Specifically, increased levels of C18 Cer remained significantly associated with poorer OS in the multivariate model, even after adjusting for treatment line and PSA levels (Hazard Ratio: 3.59 [95% Confidence Interval 1.51-8.52], p = 0.004). Employing quantitative mass spectrometry, our findings underscore the independent prognostic significance of C18 Cer in individuals with mCRPC. This discovery opens avenues for further studies within this field.
(© 2023. Springer Nature Limited.)
Databáze: MEDLINE
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