Inflammatory Metabolic Profile of South African Patients with Prostate Cancer

Abstract Background: Men with African ancestry are more likely to develop aggressive prostate cancer (PCa) and to die from this disease. A distinct genomic landscape associated with specific ethnic groups may lead to different metabolic adaptations and inflammatory responses that permit tumor cells to proliferate and to grow. We hypothesize that a higher risk of lethal PCa in men with African ancestry may be associated with high level of systemic inflammation. Methods: In this study, plasma samples were profiled from a cohort of 41 South African men with PCa using Nuclear Magnetic Resonance (NMR) spectroscopy. A total of 41 features, including metabolites, lipid classes, total protein, and the inflammatory NMR markers, GlycA and GlycB were quantified from each NMR spectrum. The Bruker’s B.I.-LISA protocols were used to characterize 114 parameters related to the lipoproteins, such as HDL, LDL and VLDL, and their relative subclasses. The unsupervised KODAMA method was used to stratify the patients of our cohort based on their metabolic profile. Results: We found that the plasma of patients with very high risk, aggressive PCa and high level of C-reactive protein have a peculiar metabolic phenotype (metabotype) characterized by extremely high levels of GlycA and GlycB. The inflammatory processes linked to the higher level of GlycA and GlycB are characterized by a deep change of the plasma metabolome that leads the stratification of patients with PCa. We also identified a not previously relationship between high values of very-high density lipoprotein and low level of GlycB in a different metabotype of patients characterized by lower risk PCa. Conclusions: Systemic inflammation plays a role in the metabolic profile of cancer. This study advances our understanding of the relationship between metabolome and systemic inflammation in the context of PCa and opens the door to a totally innovative approach for biomarker discovery and to the development of new therapies aiming to reduce the systemic inflammation in these patients.