Abstract 3222: Broad spectrum metabolite profiling reveals metabolic finger and footprinting which correlate to gene expression signatures of triple-negative breast cancer (TNBC).

TNBC constitutes ∼20% of all breast cancers and disproportionately affects younger women and African-American women. This genomically heterogeneous disease is defined by the lack of expression of estrogen and progesterone receptors and the lack of amplification of HER2/neu. TNBC is resistant to standard breast cancer therapies. Due to the lack of a predominant genetic lesion associated with the disease, identification of metabolic fingerprints within TNBC is a critical first step for identification of molecular drivers and development of targeted therapies. Metabolite profiling (metabolomics) of a wide range of metabolites can be used to globally profile the metabolic state of cancer cells. Nine widely used TNBC-derived cell lines already characterized by gene expression signatures were analyzed by metabolomics. Two different approaches were combined: (i) untargeted, broad profiling including LC-MS/MS and GC-MS, and (ii) targeted UPLC-MS/MS Energy platform technology which covers polar key metabolites mainly reflecting energy status and nucleotide biosynthesis. Finally, 239 high quality metabolites were statistically evaluated in cell lysates and 128 metabolites in spent media samples collected from all cell lines. Using innovative bioinformatics and data mining tools we identified metabolic alterations in energy utilization, lipid synthesis, and other pathways of importance to highly proliferative cells that differ significantly from an untransformed control cell line (MCF-10A). Major metabolic changes combining results of metabolic fingerprinting and footprinting and their biological relevance will be discussed. Citation Format: Alexander Beatty, Lauren Fink, Alexander Strigun, Ulrike Rennefahrt, Oliver Schmitz, Hajo Schiewe, Niels Moeller, Patricia R. Noppinger, Regina Reszka, Jeffrey R. Peterson. Broad spectrum metabolite profiling reveals metabolic finger and footprinting which correlate to gene expression signatures of triple-negative breast cancer (TNBC). [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 3222. doi:10.1158/1538-7445.AM2013-3222