Metabonomic changes from pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma in tissues from rats

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and is difficult to diagnose in the early phase. This study was aimed at obtaining the metabolic profiles and characteristic metabolites of pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues from Sprague-Dawley (SD) rats to establish metabonomic methods used in the early diagnosis of PDAC. In the present study, the animal models were established by embedding 7,12-dimethylbenzanthracene (DMBA) in the pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, (1) H nuclear magnetic resonance (NMR) spectroscopy combined with multivariate and univariate statistical analysis was applied to identify the potential metabolic signatures and the corresponding metabolic pathways. Pattern recognition models were successfully established and differential metabolites, including glucose, amino acids, carboxylic acids and coenzymes, were screened out. Compared with the control, the trends in the variation of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, thus, could served as biomarkers to distinguish PanIN from PDAC. Our results suggest that NMR-based techniques combined with multivariate statistical analysis can distinguish the metabolic differences among PanIN, PDAC and normal tissues, and, therefore, present a promising approach for physiopathologic metabolism investigations and early diagnoses of PDAC.