Abstract 4541: Metabolomic diagnosis of prostate cancer from urine

Abstract

Abstract There is a critical unmet need for new diagnostic tests to both determine if a patient has prostate cancer and whether that cancer is aggressive and therefore requires aggressive management. In this study we performed global metabolomic profiling on the post-DRE urine sediments of twenty-four men referred to the urologist with concern of prostate cancer. Eight of these men presented with benign prostatic conditions leading to a raised PSA while the remaining sixteen patients had clinical T3 prostate cancer. Global metabolomic profiling was carried out on methanolic extracts of these urine sediments. The resulting data sets were found to contain 256 metabolites based on spectral comparison against an in-house chemical reference library of over 2500 authentic standards. A subset of prostate cancer patients, but no patients with benign prostatic conditions, had elevated sarcosine abundance in their urine sediments. Patients with elevated sarcosine had a distinct metabolic signature that included sixty-five other differentially abundant metabolites, predominantly amino acids and their catabolites, differentiating these patients from the rest. The remaining prostate cancer patients could be differentiated from the patients with benign prostatic conditions based on their abundance profiles of acyl carnitines (increased) and uridine (reduced). Stable isotope dilution assays for select analytes confirmed these results, and several multianalyte algorithms were found to have good performance for the diagnosis of prostate cancer (AUROC > 0.8). Both metabolic presentations of prostate cancer exhibited biochemical hallmarks of multiple acyl-coA dehydrogenase deficiency, an inborn error of metabolism that can be due to impaired activity of the mitochondrial electron transfer flavoprotein/quinone oxidase complex. These data indicate that post-DRE urine sediment profiling could provide valuable information regarding the need to refer the urologic patient for prostate biopsy and may hold additional insight into the molecular pathogenesis of prostate cancer. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 4541. doi:1538-7445.AM2012-4541