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

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant tumors and the diagnosis in early phase is quite difficult. 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 PDAC's early diagnosis. In the present study, the animal models were established by embedding 7, 12-dimethylbenzanthracene (DMBA) in pancreas of SD rats to obtain PanIN and PDAC tissues. After the preprocessing of tissues, ¹H 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. As results, 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 variation trends of several metabolites were similar in both PanIN and PDAC. Kynurenate and methionine levels were elevated in PanIN but decreased in PDAC, indicating to be specific metabolites distinguishing PanIN from PDAC. Our results suggested that the metabonomic strategy of NMR-based techniques combined with multivariate statistical analysis could distinguish the metabolic differences of PanIN, PDAC and normal, demonstrated to be a promising approach in physiopathologic metabolism investigations and early diagnoses of PDAC.

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