Jornal de Biomarcadores Moleculares e Diagnóstico

Urinary Metabolomic Analysis of Human Gastric Cancer Mouse Models and Patients Using Gas Chromatography/Mass Spectrometry

Abstract

Jin-Lian Chen, Jing Fan, Hui-Qing Tang, Jun-Duo Hu and Jian-Zhong Gu

Gastric cancer is the second cause of cancer deaths in China. To identify potential markers for screening or diagnosis of gastric cancer, we coupled xenotransplantation mouse models with a urine metabolomic approach. SGC-7901 gastric cancer cells were subcutaneously or orthotopically implanted into nude mice to establish metastasis and non-metastasis mouse models. Urine samples from mice bearing tumors or gastric cancer patients and their healthy controls were collected and subjected to gas chromatography and mass spectrometry (GC/MS) analysis. Metabolic data were analyzed using Mann-Whitney test to find urinary biomarkers for gastric cancer. Diagnostic models for gastric cancer mice and patients were constructed using principal components analysis (PCA) and validated with the area under the curve (AUC) of receiver operating characteristic (ROC) curves. The results indicated these metabolites mainly include lactic acid, serine, proline, malic acid, and fatty acids. The PCA models discriminated all gastric cancer mice or most gastric cancer patients including six of seven early stage patients, from their healthy controls with AUC value of 1.0 or 0.996, respectively. In addition, they were able to differentiate between metastatic and non-metastatic mice with AUC value of 1.0, as well as between invasive/metastatic and non-invasive cancers with AUC value of 0.982. Our data suggest that there are significant metabolic alterations during progression of gastric cancer and the potential metabolic biomarkers could be useful for screening and early diagnosis of gastric cancer progression.