Abstract 3987: Prospective serum metabolomic profiles of prostate cancer by size and extent of primary tumor
Authors: Albanes Demetrius , Weinstein Stephanie J. , Mondul Alison M. 
Published: July 2016

Abstract
Background: Recent studies have identified serum metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. Lipid and energy metabolites were significantly lower in cases vs. controls, including glycerophospholipids, inositol-1-phosphate, alpha-ketoglutarate, and citrate. To elucidate whether the findings represent an etiologic process or biomarkers of subclinical disease, we focused on differences in the prospective serum metabolomic profiles of men with T2, T3, and T4 prostate cancers.
Methods: Clinical data from a nested case-control analysis of prostate cancer in the ATBC Study cohort were examined, including 71 cases diagnosed with T2 primary cancer, 51 with T3, and 15 with T4 (all cases, ages 61-89 years at diagnosis). Median time from fasting serum collection to diagnosis was 10 yr, range 1-20 yr. Cases in each extent of disease category were compared to a common set of 200 non-case controls. Serum samples were analyzed on a high resolution accurate mass platform of ultrahigh performance liquid chromatography/mass spectroscopy and gas chromatography/mass spectroscopy (Metabolon, Inc.), and 654 known metabolites were identified. Unconditional logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for cancer associated with a one standard deviation (1-SD) increment in metabolite concentration.
Results: Among the strongest serum metabolite signals for men with T2 prostate cancers were N-acetyl-3-methylhistidine, 2-deoxyuridine, 3-methylhistidine, beta-hydroxyisovalerate, stearoylarachidonoyl-GPPE, and euricoyl-sphingomyelin [1-SD ORs 1.79, 1.71, 1.38, 1.48, 0.73, and 1.48 (p = 0.0002, 0.005, 0.01, 0.02, 0.02, and 0.02), respectively]. Men diagnosed with T3 cancer exhibited a lipid metabolite profile most similar to that previously reported for aggressive disease, with top metabolite signals being for oleoyl-linoleoyl-GPPI, palmitoyl-linoleoyl-GPPI, cholate, inositol-1-phosphate, stearoyl-sphingomyelin, and 4-imidazoleacetate (ORs 0.49, 0.56, 0.57, 0.60, 1.54, and 1.59 (p = 0.00002, 0.001, 0.002, 0.003, 0.01, and 0.01), respectively). Men with more extensive T4 cancers showed secondary bile acid and caffeine metabolite associations including orotate, taurodeoxycholate, glycodeoxycholate, caffeine, 4-imidazoleacetate, 1,3,7-trimethylurate, and deoxycholate (ORs 0.40, 2.62, 3.19, 2.40, 2.52, 2.31, and 3.31 (p = 0.004, 0.007, 0.007, 0.01, 0.01, 0.02, and 0.02), respectively).
Conclusions: In this analysis, men with T2, T3, and T4 prostate cancer primaries exhibited qualitative differences in their serum metabolite profiles years in advance of the clinical diagnoses. Whether these differences represent novel biomarkers related to greater primary tumor mass that individual patients might “transition” through while still undiagnosed is unknown but testable through additional clinical series.
Citation Format: Demetrius Albanes, Stephanie J. Weinstein, Alison M. Mondul. Prospective serum metabolomic profiles of prostate cancer by size and extent of primary tumor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 3987.