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.
| Language | English |
|---|---|
| Pages | 2112-2120 |
| Number of pages | 9 |
| Journal | International Journal of Cancer |
| Volume | 141 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 15 Nov 2017 |
| Externally published | Yes |
Fingerprint
Keywords
- biomarker
- castration-resistant
- lipids
- prognosis
- prostate cancer
Cite this
}
A Distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer. / PRIMe Consortium.
In: International Journal of Cancer, Vol. 141, No. 10, 15.11.2017, p. 2112-2120.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - A Distinct plasma lipid signature associated with poor prognosis in castration-resistant prostate cancer
AU - Lin, Hui Ming
AU - Mahon, Kate L.
AU - Weir, Jacquelyn M.
AU - Mundra, Piyushkumar A.
AU - Spielman, Calan
AU - Briscoe, Karen
AU - Gurney, Howard
AU - Mallesara, Girish
AU - Marx, Gavin
AU - Stockler, Martin R.
AU - PRIMe Consortium
AU - Parton, Robert G.
AU - Hoy, Andrew J.
AU - Daly, Roger J.
AU - Meikle, Peter J.
AU - Horvath, Lisa G.
PY - 2017/11/15
Y1 - 2017/11/15
N2 - 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.
AB - 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.
KW - biomarker
KW - castration-resistant
KW - lipids
KW - prognosis
KW - prostate cancer
UR - http://www.scopus.com/inward/record.url?scp=85029574981&partnerID=8YFLogxK
U2 - 10.1002/ijc.30903
DO - 10.1002/ijc.30903
M3 - Article
VL - 141
SP - 2112
EP - 2120
JO - International Journal of Cancer
T2 - International Journal of Cancer
JF - International Journal of Cancer
SN - 0020-7136
IS - 10
ER -