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Int J Cancer. 2017 Nov 15;141(10):2112-2120. doi: 10.1002/ijc.30903. Epub 2017 Aug 8.

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

Author information

1
Cancer Division, The Kinghorn Cancer Centre/Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
2
St Vincent's Clinical School, UNSW Sydney, NSW, Australia.
3
Medical Oncology, Chris O'Brien Lifehouse, Camperdown, NSW, Australia.
4
Royal Prince Alfred Hospital, Camperdown, NSW, Australia.
5
Metabolomics Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, VIC, Australia.
6
Medical Oncology, Mid North Coast Cancer Institute, Coffs Harbour Health Campus, Coffs Harbour, NSW, Australia.
7
Medical Oncology, Crown Princess Mary Cancer Centre, Westmead Hospital, Westmead, NSW, Australia.
8
Medical Oncology, Calvary Mater Newcastle, Waratah, NSW, Australia.
9
Medical Oncology, Sydney Adventist Hospital, Wahroonga, NSW, Australia.
10
Medical Oncology, Concord Repatriation General Hospital, Concord, NSW, Australia.
11
Sydney Medical School, The University of Sydney, Camperdown, NSW, Australia.
12
Pharmacogenomics Research for Individualised Medicine Consortium, NSW, Australia.
13
Cell Biology and Molecular Medicine Division, Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
14
Discipline of Physiology, School of Medical Sciences & Bosch Institute, Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia.
15
Biomedicine Discovery Institute and Department of Biochemistry and Molecular Biology, Monash University, Clayton, VIC, Australia.

Abstract

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.

KEYWORDS:

biomarker; castration-resistant; lipids; prognosis; prostate cancer

PMID:
28741687
DOI:
10.1002/ijc.30903
[Indexed for MEDLINE]
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