474. Metabolomic Discrimination of Intestinal- and Diffuse-type Gastric Cancer Tissues Using Capillary Electrophoresis Time-of-flight Mass Spectrometry

2012 ◽  
Vol 38 (9) ◽  
pp. 868
Author(s):  
M. Terashima ◽  
M. Kusuhara ◽  
M. Tokunaga ◽  
Y. Tanizawa ◽  
E. Bando ◽  
...  
2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e14635-e14635
Author(s):  
Masanori Terashima ◽  
Masatoshi Kusuhara ◽  
Masanori Tokunaga ◽  
Yutaka Tanizawa ◽  
Etsuro Bando ◽  
...  

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.


2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 66-66
Author(s):  
Sanae Kaji ◽  
Masatoshi Kusuhara ◽  
Rie Makuuchi ◽  
Yushi Yamakawa ◽  
Masanori Tokunaga ◽  
...  

66 Background: To explore carcinogenic and prognostic biomarkers for gastric cancer, genomics, transcriptomics and proteomics approaches have been extensively applied;however, little has been investigated regarding the role of metabolomics profiles on progression and prognosis of gastric cancer. Therefore, in order to elucidate the role of metabolome on prognosis of gastric cancer, we investigated the metabolic profiles of gastric cancer tissue using time-of-flight mass spectrometry (TOFMS) Methods: A total of 162 patients with gastric cancer underwent gastrectomy from February 2010 to March 2013 were enrolled in this study. Cancer tissues (CA) and adjacent non-cancerous tissues (NC) were obtained from surgically resected sample and were snap-frozen in liquid nitrogen. The samples were then homogenized and then applied to capillary electrophoresis TOFMS (CE-TOFMS) The metabolomics dates were analyzed using principal component analysis (PCA) and hierachical clustering analysis(HCA) in order to compare the metabolic profiles of NC and CA. Metabolites date were further assessed according by the non-parametric Mann–Whitney U-test on the presence or absence of recurrence . Results: A total 96 metabolites were detected and quantified. PCA of the date well-distinguished CA from NC. In CA, lactate / pyruvate ratio was significantly higher, while adenylate energy charge was significantly lower than NC, which reaffirms the Warburug effect of cancer. Total glutathione and reducted glutathione/oxidized glutathione ratio in CA were significantly higher than in NC which possibly contributes to the homeostasis of redox status in CA. Intriguingly, in patients with recurrence, tumor concentrations of β-Ala, Asp, GDP and Gly were significantly lower than in those without recurrence. Conclusions: Metabolomic profiling clearly differentiated CA from NC. Considerably high lactate and amino acids levels expectedly highlighted the metabolome of tumors. Certain metabolite will be a candidate for biomarker in gastric cancer.


1999 ◽  
Vol 50 (3-4) ◽  
pp. 188-194 ◽  
Author(s):  
I. M. Lazar ◽  
G. Naisbitt ◽  
M. L. Lee

Chirality ◽  
2018 ◽  
Vol 30 (9) ◽  
pp. 1079-1087 ◽  
Author(s):  
Xuezi Cui ◽  
Chen Liang ◽  
Feijun Gong ◽  
Rong Wang ◽  
Chunfang Ni ◽  
...  

2008 ◽  
Vol 80 (16) ◽  
pp. 6329-6335 ◽  
Author(s):  
Tuuli Levandi ◽  
Carlos Leon ◽  
Mihkel Kaljurand ◽  
Virginia Garcia-Cañas ◽  
Alejandro Cifuentes

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