Abstract 1860: Metabolomics for the identification of prognostic biomarkers of pancreatic cancer.

Abstract

Abstract Introduction: Although the survival outcomes of Pancreatic Ductal Adenocarcinoma (PDAC) continue to be poor, clinical and basic research in this field is disproportionately under-represented as compared to other cancer sites. Currently, there is no blood or fluid test for diagnosis or prognosis of PDAC. Sensitive and specific biomarkers are thus critical for improving clinical outcomes of PDAC. Our goal in this study was to identify molecular features that could be used for disease stratification. The underlying hypothesis was that targeted, quantitative evaluation of molecular fingerprints of PDAC in serum, calculated originally via matched tissue metabolomic profiles using an untargeted approach may have direct clinical applicability. Approach: We have used mass spectrometry based metabolomics, an emerging field that provides new information on biological perturbations based on changes in multiple endogenous metabolites. These metabolites represent the endpoint of cellular processes and are hence a direct readout of the phenotype or the physiological status. Detection of PDAC using a metabolomics approach is based on the establishment of specific key metabolite signatures in pancreatic tumor tissue derived from patients diagnosed with PDAC. A shortlisted panel of these putative markers was tested for their pre-clinical performance using serum samples from the same patients. This combinatorial approach allowed us to interrogate the PDAC tissue metabolome in a global and unbiased fashion and subsequently test the clinical applicability using a targeted approach in serum samples. Results: The untargeted metabolomics profiling resulted in the identification of a panel of key metabolites which could help discriminate PDAC tissue profiles from pancreatitis and colo-rectal tumor tissue. Validation of these metabolites in serum is ongoing. Conclusion: Our results demonstrate the power of metabolomics for developing clinical assays for diagnosis and prognosis of PDAC. Identification of cellular target molecules, associated with pancreas cancer oncogenesis, progression and metastasis is critical for designing new treatment options for advanced stage disease. Developing a specific and sensitive panel of bio-markers offers a pragmatic approach towards increasing overall survival rates; identify molecular targets for therapeutic development, improving treatment strategies and thus clinical outcomes Supported by American Cancer Society Citation Format: Keith Unger, Prabhjit Kaur, Amrita K. Cheema. Metabolomics for the identification of prognostic biomarkers of pancreatic cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1860. doi:10.1158/1538-7445.AM2013-1860