Abstract 1867: Metabolomic discrimination of undifferentiated and differentiated gastric cancer.

Clinicopathological characteristics of gastric cancer patients strongly depend on histological type. In contrast with gene and protein expressions, metabolic properties of undifferentiated (UT) and differentiated (DT) gastric cancer have been largely unknown. Here, we conducted comparative metabolome analyses in UT and DT cell lines, uncovering characteristic differences between the levels of metabolites involved in energy metabolism. The metabolomic profile of DT cell lines was featured by its considerably high glycolytic intermediate, nucleotide, and glutathione levels, which highlight hallmarks of cancer metabolism represented by the Warburg effect and hyperactive nucleotide syntheses. In contrast, UT cell lines rather showed relatively low energy and redox statuses. We further confirmed the trends by measuring 392 metabolites of paired non-tumor and tumor gastric tissues obtained pairwise from 27 gastric cancer patients in order to metabolomically characterize non-tumors, UT (n=18), and DT (n=9) tumors. The results not only distinguished the profile of non-tumors from tumors, especially of DT, but also reaffirmed the distinctions between UT and DT tumors. Taken together, UT and DT cancers were metabolomically characterized both in vitro and in vivo; DT exhibited more typical cancer metabolic profiles than UT, whereas low glutathione ratios in UT imply their vulnerability to oxidative stress, which thus could be useful for developing more subtype-specific cancer therapeutics. Citation Format: Kenjiro Kami, Tamaki Fujimori, Masanori Terashima, Masatoshi Kusuhara, Masanori Tokunaga, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Hiroyuki Yamamoto, Yoshiaki Ohashi. Metabolomic discrimination of undifferentiated and differentiated gastric 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 1867. doi:10.1158/1538-7445.AM2013-1867