Metabolomic discrimination of intestinal- and diffuse-type gastric cancer tissues using capillary electrophoresis time-of-flight mass spectrometry.

Abstract

e14635 Background: Clinicopathological characteristics of gastric cancer patients strongly depend on histological type. In contrast with gene and protein expressions, metabolic properties of intestinal- and diffuse-type gastric cancer have been largely unknown. Here, we conducted metabolome analysis of paired non-tumor and tumor gastric tissues by using capillary electrophoresis and liquid chromatography combined with time-of-flight mass spectrometry (CE- and LC-TOFMS, respectively) in order to metabolomically characterize non-tumors (NTs), intestinal-type tumors (ITs), and diffuse-type tumors (DTs). Methods: Tumor and surrounding non-tumor tissues were surgically excised pair-wise from 27 gastric cancer patients (18 ITs and 9 DTs) who underwent gastrectomy at our institution between February and May 2011. Following tissue homogenization and metabolite extraction, we measured 254 and 138 metabolites, respectively, by CE-TOFMS and LC-TOFMS. Results: Metabolomic profiles of tumor tissues, especially ITs, were well-distinguished from those of NTs: Lactate and most glycolytic intermediate levels in ITs were significantly higher than those in NTs, which reaffirms the Warburg effect of cancer, but the significance was lesser in DTs. Levels of all the measured amino acids were significantly higher in ITs and relatively higher in DTs than in NTs, showing high capacities of cancer cells for protein synthesis. Although levels of ATP, GTP, and energy charge in ITs and DTs were lower than those in NTs, purine contents were rather higher in the tumors than in NTs, which may support their high demand for DNA replication. Moreover, reduced glutathione in DTs were the lowest among others, implying their potential vulnerability against oxidative stress. Conclusions: Metabolomic profiles of NTs, ITs, and DTs were discriminated by CE- and LC-TOFMS analyses: Considerably high lactate, amino acid, and purine levels highlighted the metabolome of tumors, especially of ITs. Relatively low energy and redox statuses of DTs, however, could be targeted for developing more effective cancer therapeutics.