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 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, 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. 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.

Associations between metabolites and pancreatic cancer risk in a large prospective epidemiological study

“…This process also maintains higher reduced glutathione levels and redox balance 13 15. In previous metabolomic studies, blood, saliva and tumour tissue glutamate concentrations have been associated with PDAC in small case-control studies,16–19 and rodent studies have shown higher glutamate concentrations in blood and pancreatic tissue from pancreatic intraepithelial neoplasia and PDAC compared with control animals 20 21. These studies show less consistent associations for aspartate 21 22…”

Recent Advances in NMR-Based Metabolomics

“…112,113 Investigations of pancreatic cancer using animal models have been made based on metabolite profiling of tissue extract and serum. 114,115 The disease model included both pancreatic intraepithelial neoplasia and pancreatic ductal adenocarcinoma and the results showed significant differences in metabolite profiles between the two pathological conditions. In the area of ovarian cancer, ovarian cyst fluid samples from benign, borderline, and malignant ovarian tumors were investigated.…”

Identification and functional analyses of differentially expressed metabolites in early stage endometrial carcinoma

“…Metabolomics, a noninvasive diagnostic technology that focuses on the metabolite profiles involved in disease perturbations and provides a characteristic fingerprint in disease, has been applied to clinical studies of many diseases, including different cancers . It is regarded to be a sensitive, accurate and high‐throughput platform for cancer diagnosis, prognostic evaluation and clinical trials, and ultra‐high performance liquid chromatography quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF/MS) technology has been widely used for metabolite profiling in various clinical samples (eg, in serum and urine).…”