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Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer

Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia
St Vincent’s Clinical School, UNSW Sydney (the University of New South Wales), Darlinghurst, NSW 2010, Australia
The Kinghorn Cancer Centre, St Vincent’s Hospital, Darlinghurst, NSW 2010, Australia
Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia
Department of Medical Oncology, Monash Health, Clayton, VIC 3168, Australia
Department of Medicine, School of Clinical Sciences, Monash University, Clayton, VIC 3168, Australia
Eastern Health Clinical School, Monash University, Box Hill, VIC 3128, Australia
Cancer Services, Eastern Health, Box Hill, VIC 3128, Australia
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia
Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, VIC 3000, Australia
Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia
Royal Prince Alfred Hospital, Camperdown, NSW 2050, Australia
Faculty of Medicine and Health, University of Sydney, Camperdown, NSW 2050, Australia
Concord Cancer Centre, Concord Repatriation General Hospital, Concord, NSW 2139, Australia
Mid North Coast Cancer Institute, Coffs Harbour, NSW 2450, Australia
SAN Integrated Cancer Centre, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia
Medical Oncology, St George Hospital, Kogarah, NSW 2217, Australia
Author to whom correspondence should be addressed.
Academic Editor: David Wong
Cancers 2021, 13(19), 4964;
Received: 30 August 2021 / Revised: 27 September 2021 / Accepted: 27 September 2021 / Published: 1 October 2021
(This article belongs to the Special Issue Advances in Companion Biomarker Development for Prostate Cancer)
Lipids (fatty substances) and cytokines are molecules that affect how the immune response works. The measurement of the amounts of lipids and cytokines in blood might give clues about how prostate cancers grow or respond to treatment. This study looked at the blood levels of lipids and cytokines in men with advanced prostate cancer that was growing despite standard treatment (metastatic castration-resistant prostate cancer, mCRPC). We found that certain lipids were consistently associated with poorer clinical outcome, while cytokines were not. The levels of a type of lipid (ceramide) were associated with some cytokines. This lipid is known to activate the immune system and is associated with poor outcomes in mCRPC. A change in lipid profiles was associated with better response to treatment. Overall, our findings suggest that blood lipids might be more informative than cytokines, might influence the immune response, and might help predict treatment response.
Circulating lipids or cytokines are associated with prognosis in metastatic castration-resistant prostate cancer (mCRPC). This study aimed to understand the interactions between lipid metabolism and immune response in mCRPC by investigating the relationship between the plasma lipidome and cytokines. Plasma samples from two independent cohorts of men with mCRPC (n = 146, 139) having life-prolonging treatments were subjected to lipidomic and cytokine profiling (290, 763 lipids; 40 cytokines). Higher baseline levels of sphingolipids, including ceramides, were consistently associated with shorter overall survival in both cohorts, whereas the associations of cytokines with overall survival were inconsistent. Increasing levels of IL6, IL8, CXCL16, MPIF1, and YKL40 correlated with increasing levels of ceramide in both cohorts. Men with a poor prognostic 3-lipid signature at baseline had a shorter time to radiographic progression (poorer treatment response) if their lipid profile at progression was similar to that at baseline, or their cytokine profile at progression differed to that at baseline. In conclusion, baseline levels of circulating lipids were more consistent as prognostic biomarkers than cytokines. The correlation between circulating ceramides and cytokines suggests the regulation of immune responses by ceramides. The association of treatment response with the change in lipid profiles warrants further research into metabolic interventions. View Full-Text
Keywords: circulating lipids; cytokines; metastatic castration-resistant prostate cancer; lipidomic; biomarkers circulating lipids; cytokines; metastatic castration-resistant prostate cancer; lipidomic; biomarkers
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MDPI and ACS Style

Lin, H.-M.; Yeung, N.; Hastings, J.F.; Croucher, D.R.; Huynh, K.; Meikle, T.G.; Mellett, N.A.; Kwan, E.M.; Davis, I.D.; Tran, B.; Mahon, K.L.; Zhang, A.; Stockler, M.R.; Briscoe, K.; Marx, G.; Bastick, P.; Crumbaker, M.L.; Joshua, A.M.; Azad, A.A.; Meikle, P.J.; Horvath, L.G. Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer. Cancers 2021, 13, 4964.

AMA Style

Lin H-M, Yeung N, Hastings JF, Croucher DR, Huynh K, Meikle TG, Mellett NA, Kwan EM, Davis ID, Tran B, Mahon KL, Zhang A, Stockler MR, Briscoe K, Marx G, Bastick P, Crumbaker ML, Joshua AM, Azad AA, Meikle PJ, Horvath LG. Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer. Cancers. 2021; 13(19):4964.

Chicago/Turabian Style

Lin, Hui-Ming, Nicole Yeung, Jordan F. Hastings, David R. Croucher, Kevin Huynh, Thomas G. Meikle, Natalie A. Mellett, Edmond M. Kwan, Ian D. Davis, Ben Tran, Kate L. Mahon, Alison Zhang, Martin R. Stockler, Karen Briscoe, Gavin Marx, Patricia Bastick, Megan L. Crumbaker, Anthony M. Joshua, Arun A. Azad, Peter J. Meikle, and Lisa G. Horvath. 2021. "Relationship between Circulating Lipids and Cytokines in Metastatic Castration-Resistant Prostate Cancer" Cancers 13, no. 19: 4964.

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