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

Cancers

Edmond M. Kwan¹  Ian D. Davis²  Nicole Yeung³  Hui-Ming Lin³  Lisa G. Horvath³  Megan L. Crumbaker³  Jordan F. Hastings³  Kate L. Mahon³  Anthony M. Joshua³  David R. Croucher³  Alison Zhang⁴  Martin R. Stockler⁴  Patricia Bastick⁵  Peter J. Meikle⁶  Thomas G. Meikle⁶  Natalie A. Mellett⁶  Kevin Huynh⁶  Karen Briscoe⁷  Gavin Marx⁸  Ben Tran⁹  Arun A. Azad⁹ 

[1] Department of Medical Oncology, Monash Health, Clayton, VIC 3168, Australia;Eastern Health Clinical School, Monash University, Box Hill, VIC 3128, Australia;Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia;Medical Oncology, Chris O’Brien Lifehouse, Camperdown, NSW 2050, Australia;Medical Oncology, St George Hospital, Kogarah, NSW 2217, Australia;Metabolomics Laboratory, Baker Heart and Diabetes Institute, Melbourne, VIC 3004, Australia;Mid North Coast Cancer Institute, Coffs Harbour, NSW 2450, Australia;SAN Integrated Cancer Centre, Sydney Adventist Hospital, Wahroonga, NSW 2076, Australia;Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3010, Australia;

关键词: circulating lipids;    cytokines;    metastatic castration-resistant prostate cancer;    lipidomic;    biomarkers;   

DOI  :  10.3390/cancers13194964

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown