Toxicometabolomics of Urinary Biomarkers for Human Gastric Cancer in a Mouse Model
Toxicometabolomics of Urinary Biomarkers for Human Gastric Cancer in a Mouse Model
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DOI：
10.1080/15287394.2010.511545
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发表时间：
2010-01-01
影响因子：
2.6
通讯作者：
Lee, Byung Mu
中科院分区：
文献类型：
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作者：
Kim, Kyu-Bong;Yang, Ji-Young;Lee, Byung Mu
使用 1H 核磁共振 (NMR) 波谱研究了小鼠模型中人胃癌尿液生物标志物的毒理学代谢组学。将人胃腺癌细胞系（1 x 107 个细胞/ml）移植到完整雄性 BALB/c-nu/nu 小鼠背部的皮肤上。异种移植肿瘤形成后，收集尿液并分析内源代谢物。整体分析与主成分分析 (PCA)、偏最小二乘判别分析 (PLS-DA) 和潜在平方判别分析 (OPLS-DA) 的正交投影相结合，显示对照小鼠和荷瘤小鼠之间的簇明显分离。靶向分析显示，与正常小鼠相比，携带人胃癌细胞的小鼠的三甲胺氧化物 (TMAO)、3-吲哚硫酸、马尿酸盐和柠檬酸盐水平发生显着变化。荷瘤小鼠尿样中TMAO（0.41倍）和马尿酸盐（0.26倍）的水平显着降低，而3-吲哚硫酸盐（3.39倍）、2-酮戊二酸盐（2.32倍）和柠檬酸盐（1.9倍）的水平显着升高。数据表明，TMAO、马尿酸盐、3-吲哚硫酸盐、2-酮戊二酸盐和柠檬酸盐可以作为小鼠模型中胃肿瘤发生的有用的尿液生物标志物。
Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model was investigated using 1H-nuclear magnetic resonance (NMR) spectroscopy. A human gastric adenocarcinoma cell line (1 x 107 cells/ml) was grafted onto the skin of the back of intact male BALB/c-nu/nu mice. After the xenografted tumors developed, urine was collected and analyzed for endogenous metabolites. Global profiling combined with principal components analysis (PCA), partial least squares-discriminant analysis (PLS-DA), and orthogonal projections to latent squares-discriminant analysis (OPLS-DA) showed distinct separation of clusters between control and tumor-bearing mice. Targeted profiling revealed significant changes in trimethylamine oxide (TMAO), 3-indoxylsulfate, hippurate, and citrate levels in mice carrying human gastric cancer cells compared to normal mice. The levels of TMAO (0.41-fold) and hippurate (0.26-fold) in tumor-bearing mice were significantly decreased, whereas the levels of 3-indoxylsulfate (3.39-fold), 2-oxoglutarate (2.32-fold), and citrate (1.9-fold) were significantly increased in urine samples of tumor-bearing mice. Data suggest that TMAO, hippurate, 3-indoxylsulfate, 2-oxoglutarate, and citrate may serve as useful urinary biomarkers for gastric tumorigenesis in a mouse model.