Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model.
Toxicometabolomics of urinary biomarkers for human gastric cancer in a mouse model was investigated using (1)H-nuclear magnetic resonance (NMR) spectroscopy. A human gastric adenocarcinoma cell line (1 × 10(7) 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.
Kim
Kyu-Bong
KB
Department of Pharmaceutical Engineering, Inje University, Obang-dong, Gimhae, Gyungnam, Korea.
Yang
Ji-Young
JY
Kwack
Seung Jun
SJ
Park
Kui Lea
KL
Kim
Hyung Sik
HS
Ryu
Do Hyun
DH
Kim
Yeon-Joo
YJ
Hwang
Geum-Sook
GS
Lee
Byung Mu
BM
D000230:Adenocarcinoma / Q000175:diagnosis / Q000652:urine*; D000818:Animals; D014408:Biomarkers, Tumor / Q000652:urine*; D045744:Cell Line, Tumor; D019343:Citric Acid / Q000652:urine; D016002:Discriminant Analysis; D004195:Disease Models, Animal; D006626:Hippurates / Q000652:urine; D006801:Humans; D007200:Indican / Q000652:urine; D007656:Ketoglutaric Acids / Q000652:urine; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics / Q000379:methods*; D008744:Methylamines / Q000652:urine; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D025341:Principal Component Analysis; D013274:Stomach Neoplasms / Q000175:diagnosis / Q000652:urine*; D023041:Xenograft Model Antitumor Assays
D014408:Biomarkers, Tumor; D006626:Hippurates; D007656:Ketoglutaric Acids; D008744:Methylamines; D019343:Citric Acid; C005855:trimethyloxamine; D007200:Indican; C030514:hippuric acid