Aim: To elucidate the underlying mechanisms of metastasis and to identify the metabolomic markers of gastric cancer metastasis.
Methods: Gastric tumors from metastatic and non-metastatic groups were used in this study. Metabolites and different metabolic patterns were analyzed by gas chromatography, mass spectrometry and principal components analysis (PCA), respectively. Differentiation performance was validated by the area under the curve (AUC) of receiver operating characteristic curves.
Results: Twenty-nine metabolites were differentially expressed in animal models of human gastric cancer. Of the 29 metabolites, 20 were up-regulated and 9 were down-regulated in metastasis group compared to non-metastasis group. PCA models from the metabolite profiles could differentiate the metastatic from the non-metastatic specimens with an AUC value of 1.0. These metabolites were mainly involved in several metabolic pathways, including glycolysis (lactic acid, alaline), serine metabolism (serine, phosphoserine), proline metabolism (proline), glutamic acid metabolism, tricarboxylic acid cycle (succinate, malic acid), nucleotide metabolism (pyrimidine), fatty acid metabolism (docosanoic acid, and octadecanoic acid), and methylation(glycine). The serine and proline metabolisms were highlighted during the progression of metastasis.
Conclusion: Proline and serine metabolisms play an important role in metastasis. The metabolic profiling of tumor tissue can provide new biomarkers for the treatment of gastric cancer metastasis.