title: Metabolomic and transcriptomic profiling of human K-ras oncogene transgenic rats with pancreatic ductal adenocarcinomas.
abstract: Pancreatic ductal adenocarcinoma (PDAC) is one of the most debilitating malignancies in humans, and one of the reasons for this is the inability to diagnose this disease early in its development. To search for biomarkers that can be used for early diagnosis of PDAC, we established a rat model of human PDAC in which expression of a human K-ras(G12V) oncogene and induction of PDAC are regulated by the Cre/lox system. In the present study, transgenic rats bearing PDAC and control transgenic rats with normal pancreatic tissues were used for metabolomic analysis of serum and pancreatic tissue by non-targeted and targeted gas chromatography-mass spectrometry and transcriptomic analysis of pancreatic tissue by microarray. Comparison of the metabolic profiles of the serum and pancreatic tissue of PDAC-bearing and control rats identified palmitoleic acid as a metabolite, which was significantly decreased in the serum of PDAC-bearing animals. Transcriptomic analysis indicated that several transcripts involved in anaerobic glycolysis and nucleotide degradation were increased and transcripts involved in the trichloroacetic acid cycle were decreased. Other transcripts that were changed in PDAC-bearing rats were adenosine triphosphate citrate lyase (decreased: fatty acid biosynthesis), fatty acid synthase (increased: fatty acid biosynthesis) and arachidonate 5-lipoxygenase activating protein (increased: arachidonic acid metabolism). Overall, our results suggest that the decreased serum levels of palmitoleic acid in rats with PDAC was likely due to its decrease in pancreatic tissue and that palmitoleic acid should be investigated in human samples to assess its diagnostic significance as a serum biomarker for human PDAC.
authors: Environmental Health Science Laboratory, Sumitomo Chemical Co., Osaka 554-8558, Japan. yabushitas@sc.sumitomo-chem.co.jp
authors: Setsuko
authors: S
authors: Yabushita
authors: Katsumi
authors: K
authors: Fukamachi
authors: Hajime
authors: H
authors: Tanaka
authors: Takako
authors: T
authors: Fukuda
authors: Kayo
authors: K
authors: Sumida
authors: Yoshihito
authors: Y
authors: Deguchi
authors: Kazuki
authors: K
authors: Mikata
authors: Kazuhiko
authors: K
authors: Nishioka
authors: Satoshi
authors: S
authors: Kawamura
authors: Satoshi
authors: S
authors: Uwagawa
authors: Masumi
authors: M
authors: Suzui
authors: David B
authors: DB
authors: Alexander
authors: Hiroyuki
authors: H
authors: Tsuda
mesh_terms: D058927:5-Lipoxygenase-Activating Proteins / Q000096:biosynthesis; D000230:Adenocarcinoma / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood / Q000235:genetics; D021441:Carcinoma, Pancreatic Ductal / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D064429:Fatty Acid Synthases / Q000096:biosynthesis; D005229:Fatty Acids, Monounsaturated / Q000097:blood*; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression; D020869:Gene Expression Profiling; D011905:Genes, ras / Q000235:genetics*; D006019:Glycolysis / Q000235:genetics; D006801:Humans; D055432:Metabolomics; D009711:Nucleotides / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D051381:Rats; D055647:Rats, Transgenic; D046888:Tissue Array Analysis
chemical_list: D058927:5-Lipoxygenase-Activating Proteins; D014408:Biomarkers, Tumor; D005229:Fatty Acids, Monounsaturated; D009711:Nucleotides; C008757:palmitoleic acid; D064429:Fatty Acid Synthases