Abstract 1634: Metabolomic profiling for early detection of colorectal neoplasia

Abstract

Abstract Introduction: Colorectal cancer (CRC) is the 3rd leading cause of cancer-related deaths in the world. Colonoscopy is widely used for early detection and removal of colorectal neoplasia to prevent CRC. However, it is both invasive and costly underscoring the need for new strategies to identify subjects for whom colonoscopy is most appropriate. Metabolomics is a high throughput method of detecting small molecules which provides a platform for identifying novel biomarkers of colorectal neoplasia. In this study, we investigated whether metabolic changes could be identified in the feces and plasma in a model of experimental CRC. Methods: Five week old male A/J mice were administered six weekly intraperitoneal injections of either azoxymethane (AOM) (10mg/kg) (n=40) or 0.9% saline (n=35). Following injections, feces, plasma and tumor tissue or normal colonic mucosa were collected and stored at −80oC for metabolomic analysis. Five mice from the AOM injected group were sacrificed at each of three time points (three, five and seven weeks after the last injection) to assess tumor burden. UPLC/MS/MS and GC/MS were used to quantify metabolite levels in feces, plasma and tissue. Results: Histological analysis of tumor burden in the colon showed a progressive increase as a function of time after AOM administration. Metabolomic analysis revealed a large number of significantly changed metabolite levels in both the feces and plasma during colon carcinogenesis. These included amino acids and peptides in feces as well as bile acids in the plasma. A select number of these metabolites were found to progressively change as a function of time in both feces and plasma in relation to increased tumor burden. Significantly, certain metabolites changed in the same direction in feces and tumor tissue, plasma and tumor tissue as well as across all three matrices, suggesting that these may be tumor-derived. For example, samples from AOM injected mice showed increased levels of sarcosine and 2-hydroxyglutarate, metabolites previously implicated in prostate cancer and gliomas/AML, respectively. Conclusions: This study demonstrates the potential utility of metabolomic analyses for the early detection of colorectal neoplasia. Additionally, the finding of increased levels of two onco-metabolites (sarcosine, 2-hydroxyglutarate) in colorectal neoplasia suggests their potential involvement in colon carcinogenesis. Future studies in humans will be required to determine the significance of these findings. 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 1634. doi:1538-7445.AM2012-1634