Abstract 4802: Metabolic distinctions in high grade epithelial ovarian cancer

Abstract

Abstract Objective: To identify differences in overall metabolite profile of human high grade serous epithelial ovarian cancers (EOC) compared to normal ovarian tissues. Methods: Forty-five patient tissues were obtained (n= 30 EOC, n= 15 normal). Samples were analyzed by Gas Chromatography (GC)/mass spectrometry (MS) and Liquid Chromatography (LC)/MS platforms. The difference between the groups was reported in fold change (FC). Welch's two sample t-tests were used to identify metabolites that differed significantly between cancer and normal ovarian tissues and p<0.05 was defined as significant. Results: Using an existing library containing >2000 metabolites, there were 315 metabolites that were identified between EOC and normal ovaries. Of these 315 metabolites, 204 were significantly altered with 180 up regulated metabolites, and 24 down regulated. EOC had altered metabolism in the glycolytic, amino acid, lipid, nucleotide and eicosanoid pathways. There was an increase dependence on glycolysis consistent with the “Warburg effect,” as noted by elevated glucose-6-phosphate (FC= 2.8, p<0.003), fructose-6-phosphate (FC=2.9, p<0.001) and lactate (FC= 1.7, p=0.013). Ovarian cancer cells showed significantly elevated levels of long-chain fatty acids (e.g, docosatrienoate (22:3n3) [FC= 9.06, p < 0.001), including those derived from the diet (linoleate [FC=2.25, p<0.001] and linolenate [FC=2.37, p<0.001]). Furthermore, significantly high levels of components needed for phospholipid biosynthetic pathway (e.g. cytidine 5′-diphosphocholine [16.86, p < 0.001], choline [FC = 1.5, p<0.001]) were seen which along with the altered lipid metabolism supports membrane biosynthesis in cancer cells. The eicosanoid metabolism pathway had significantly higher levels of pro-inflammatory compounds such as prostaglandins E2 (FC= 17.11, p<0.001), I2 (FC=16.35, p<0.001) and 6-keto prostaglandin F1-α (FC= 16.77, p<0.001). Interestingly, compounds best characterized only in the central nervous system, were also significantly elevated in ovarian cancer tissues. Conclusion: High grade EOC shows distinct metabolic alterations compared to normal ovarian tissues, forming the basis for targeting key metabolic pathways for biomarker and/or therapeutic approaches in ovarian 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 4802. doi:1538-7445.AM2012-4802