Metabolome analyses in human gastric cancer tissue using capillary electrophoresis time-of-flight mass spectrometry.

Abstract

61 Background: In order to explore carcinogenic and prognostic biomarkers for gastric cancer, genomic, transcriptomic and proteomic approach had been extensively investigated. However, little information is possible for metabolomics profiles in gastric cancer. As cancer cells demonstrates distinguishable growth pattern from normal cells, presence of specific metabolic pathway in cancer cells is expected. Therefore, we investigated the metabolme profiles of gastric cancer tissue by capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS). Methods: Twenty seven patients with gastric cancer underwent gastrectomy were enrolled in this study. Cancer tissue and adjacent non-cancerous tissue were obtained from surgically resected sample and immediately frozen. Frozen tissues were homogenized and then applied to CF-TOFMS.The metabolomics data by CE-TOFMS were analyzed using principal component analysis (PCA) in order to compare the metabolic profiling of the non cancerous and the cancer tissues. Correlation between metabolic profile and clinicopathologic factors were also investigated. Results: A total of 245 metabolites were detected and quantified. In PCA, the first component separated the cancer tissue data from the non-cancerous tissue data. Metabolic data from cancer tissues showed severe heterogeneity. PCA based on the difference between cancer tissue and non-cancerous tissue revealed that metabolic profile of gastric cancer was classified into two groups. One cancer group (group 1) accumulated lactate and most amino acids excessively, and another group (group 2) didn’t. In group 1, the adenylate energy charge of the cancer tissues was maintained compared to that of the non-cancerous tissues.In comparison with clinicopathologic factors, only histological type demonstrated significant correlation with metabolic classification. Undifferentiated type was significantly predominant in group 2. Conclusions: Gastric cancer was classified into two groups by quantitative metabolome profiling. As this classification significantly correlated with histological type, existence of specific metabolic pathway related to histological type is suggested.