Pre-diagnostic Serum Metabolomic Profiling of Prostate Cancer Survival.

Impaired metabolism may play a role in the development and lethality of prostate cancer, yet a comprehensive analysis of the interrelationships appears lacking. We measured 625 metabolites using ultrahigh performance LC/MS-GC/MS of prediagnostic serum from 197 prostate cancer cases in the ATBC Study (ages at diagnosis, 55-86 years). Cox proportional hazards models estimated associations between circulating metabolites and prostate cancer mortality for 1-standard deviation (SD) differences (log-metabolite scale), adjusted for age, year of diagnosis, and disease stage. Associations between metabolite chemical classes and survival were examined through pathway analysis, and Cox models assessed the relationship with a sterol/steroid metabolite principal component analysis factor score. Elevated serum N-oleoyl taurine was significantly associated with prostate cancer-specific mortality (HR=1.72 per 1-SD, p<0.00008, Bonferroni corrected threshold=0.05/625; HR=3.6 for highest vs lowest tertile, p<0.001). Pathway analyses revealed a statistically significant association between lipids and prostate cancer death (p<0.006, Bonferroni-corrected threshold=0.05/8), and sterol/steroid metabolites showed the strongest chemical sub-class association (p=0.0014, Bonferroni-corrected threshold=0.05/45). In the principal component analysis, a 1-SD increment in the sterol/steroid metabolite score increased the risk of prostate cancer death by 46%. Prediagnostic serum N-oleoyl taurine and sterol/steroid metabolites were associated with prostate cancer survival.