A distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer: Authors

Lipids are known to influence tumour growth, inflammation, and chemoresistance. However, the association of circulating lipids with the clinical outcome of metastatic castration-resistant prostate cancer (CRPC) is unknown. We investigated associations between the plasma lipidome and clinical outcome in CRPC. Lipidomic profiling by liquid chromatography-tandem mass spectrometry was performed on plasma samples from a Phase 1 discovery cohort of 96 CRPC patients. Results were validated in an independent Phase 2 cohort of 63 CRPC patients. Unsupervised analysis of lipidomic profiles (323 lipid species) classified the Phase 1 cohort into two patient subgroups with significant survival differences (HR 2.31, 95% CI 1.44-3.68, P=0.0005). The levels of 46 lipids were individually prognostic, and were predominantly sphingolipids with higher levels associated with poor prognosis. A prognostic three-lipid signature was derived (ceramide d18:1/24:1, sphingomyelin d18:2/16:0, phosphatidylcholine 16:0/16:0), and was also associated with shorter survival in the Phase 2 cohort (HR 4.8, 95% CI 2.06-11.1, P=0.0003). The signature was an independent prognostic factor when modelled with clinicopathological factors or metabolic characteristics. The association of plasma lipids with CRPC prognosis suggests a possible role of these lipids in disease progression. Further research is required to determine if therapeutic modulation of the levels of these lipids by targeting their metabolic pathways may improve patient outcome. This article is protected by copyright. All rights reserved.

International journal of cancer. 2017 Jul 25 [Epub ahead of print]

H-M Lin, K L Mahon, J M Weir, P A Mundra, C Spielman, K Briscoe, H Gurney, G Mallesara, G Marx, M R Stockler, PRIMe Consortium, R G Parton, A J Hoy, R J Daly, P J Meikle, L G Horvath

Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, New South Wales, 2010, Australia., Baker IDI Heart and Diabetes Institute, Melbourne, Victoria, 3004, Australia., Mid North Coast Cancer Institute, Coffs Harbour Health Campus, Coffs Harbour, New South Wales, 2450, Australia., Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, New South Wales, 2145, Australia., Calvary Mater Newcastle, Waratah, New South Wales, 2298, Australia., Sydney Adventist Hospital, Wahroonga, New South Wales, 2076, Australia., Chris O'Brien Lifehouse, Camperdown, New South Wales, 2050, Australia., Pharmacogenomics Research for Individualised Medicine Consortium (www.prime.org.au), New South Wales, Australia., Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, 4072, Australia., Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, 2050, Australia., Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, 3800, Australia.