Quantitative measurement of organic acids in tissues from gastric cancer patients indicates increased glucose metabolism in gastric cancer.

Abstract

The levels of organic acids representing metabolic pathway end products are

important indicators of physiological status, and may be associated with

metabolic changes in cancer. The aim of this study is to investigate the levels

of organic acids in cancerous and normal tissues from gastric cancer patients and

to confirm the role of metabolic alterations in gastric carcinogenesis. Organic

acids in normal and cancerous tissues from forty-five patients with gastric

adenocarcinoma were investigated by gas chromatography-mass spectrometry in

selected ion monitoring mode as methoxime/tert-butyldimethylsilyl derivatives. We

analysed the significant differences in the levels of organic acids in normal and

cancer tissues and investigated the correlation of these levels in cancer tissues

with clinicopathological features. The levels of Krebs cycle components,

including alpha-ketoglutaric acid, succinic acid, fumaric acid, malic acid and

oxaloacetic acid, were significantly increased in cancer tissues compared to

normal tissues. In addition, the levels of glycolytic products, including pyruvic

acid and lactic acid, as well as the levels of ketone bodies, including

3-hydroxybutyric acid, were also significantly increased in cancer tissues

compared to normal tissues. The levels of ketone bodies in cancer tissues with

differentiated histology and in intestinal-type cancer tissues were significantly

increased. The organic acid profiling analysis described here may be a generally

useful clinical tool for understanding the complexity of metabolic events in

gastric adenocarcinoma, and organic acids may have potential as metabolic markers

for the future discovery of diagnostic and therapeutic modalities.