Abstract
Abstract Introduction and Objective Recently it has been shown that many oncogenes regulate metabolism, revitalizing interest in Warburg's observation of aerobic glycolysis by tumors. We and others have demonstrated the utility of metabolic signatures for the diagnosis of cancer in minimally invasive clinical samples and the differential diagnosis of cancer by stage and grade using biopsy samples. Here we apply state of the art metabolomic analysis to the diagnosis of bladder cancer from urine samples. Methods A case controlled study of ten transitional cell carcinoma (TCC) patients and matched non-TCC controls was performed. Briefly, clarified urine was extracted into aqueous methanol and characterized using three analytical platforms (gas chromatography mass spectrometry (MS) and ultrahigh performance liquid chromatography tandem MS). Spectral data were compared against an in-house library of over 2500 authentic standards and the relative abundance of each compound within the data set was calculated. Two-group statistics (R) and multivariate analysis (Array Studio, OmicSoft) were performed to identify differentially abundant metabolites. Results Three hundred and sixty-seven compounds were identified in this study and polypharmacy did not compromise the quality of the signal obtained for endogenous metabolites. Thirteen compounds, arising from diverse metabolic pathways, including: energetics, oxidative stress and amino acid catabolism, exhibited statistically significant differences between TCC and non-TCC cases. Principal component (PC) analysis demonstrated that the majority of the information in these metabolites (PC 1) separated TCC from non-TCC cases. Conclusions These data indicate the feasibility of a novel, non-invasive, urine-based diagnostic test to detect the presence of bladder tumors. Such a test could be positioned for use in conjunction with the current standard of care to improve patient management. 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 LB-86. doi:1538-7445.AM2012-LB-86
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