title: 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, (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.
authors.affiliation: Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Wen
authors.affiliation: Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, China.
authors.forename: Zhishui
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Electronic Science, Fujian Provincial Key Laboratory of Plasma and Magnetic Resonance, Xiamen University, Xiamen, China.
authors.forename: Jianghua
authors.initials: J
authors.lastname: Feng
authors.affiliation: Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Jianxi
authors.initials: J
authors.lastname: Bai
authors.affiliation: Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Xianchao
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Fujian Medical University Union Hospital, Fuzhou, China.
authors.forename: Heguang
authors.initials: H
authors.lastname: Huang
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D002278:Carcinoma in Situ / Q000097:blood / Q000378:metabolism*; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000378:metabolism*; D055088:Early Detection of Cancer; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055432:Metabolomics; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000097:blood / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D014408:Biomarkers, Tumor
keywords: Biomarker; metabonomics; nuclear magnetic resonance; pancreatic cancer; pancreatic intraepithelial neoplasia