Department of Gastroenterology, Shanghai Sixth People's Hospital, Shanghai Jiao Tong University, 600 Yishan Road, Shanghai 200233, China.
World J Gastroenterol. 2010 Dec 14;16(46):5874-80. doi: 10.3748/wjg.v16.i46.5874.
To elucidate the underlying mechanisms of metastasis and to identify the metabolomic markers of gastric cancer metastasis.
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.
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.
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.
阐明转移的潜在机制，并确定胃癌转移的代谢组学标志物。
本研究使用转移性和非转移性组的胃肿瘤。通过气相色谱、质谱和主成分分析（PCA）分别分析代谢物和不同的代谢模式。通过接受者操作特征曲线（ROC）的曲线下面积（AUC）验证区分性能。
在人胃癌动物模型中发现 29 种代谢物存在差异表达。与非转移组相比，29 种代谢物中有 20 种在转移组中上调，9 种下调。来自代谢物谱的 PCA 模型可以区分转移性和非转移性标本，AUC 值为 1.0。这些代谢物主要涉及几种代谢途径，包括糖酵解（乳酸、碱性）、丝氨酸代谢（丝氨酸、磷酸丝氨酸）、脯氨酸代谢（脯氨酸）、谷氨酸代谢、三羧酸循环（琥珀酸、苹果酸）、核苷酸代谢（嘧啶）、脂肪酸代谢（二十二烷酸、十八烷酸）和甲基化（甘氨酸）。丝氨酸和脯氨酸代谢在转移过程中突出。
脯氨酸和丝氨酸代谢在转移中起重要作用。肿瘤组织的代谢谱可以为胃癌转移的治疗提供新的生物标志物。
