Toxicometabolomics of Urinary Biomarkers for Human Gastric Cancer in a Mouse Model

Abstract

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 × 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.

This study was supported by grants from the Korea Food and Drug Administration (KFDA) and the Korean Ministry of Education, Science and Technology and from the Korea Basic Science Institute (T30613).

Notes

Kyu-Bong Kim and Ji-Young Yang contributed equally to this article.