title: Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis.
abstract: Gastric cancer (GC) is one of the most malignant tumors with a poor prognosis. Alterations in metabolic pathways are inextricably linked to GC progression. However, the underlying molecular mechanisms remain elusive. We performed NMR-based metabolomic analysis of sera derived from a rat model of gastric carcinogenesis, revealed significantly altered metabolic pathways correlated with the progression of gastric carcinogenesis. Rats were histologically classified into four pathological groups (gastritis, GS; low-grade gastric dysplasia, LGD; high-grade gastric dysplasia, HGD; GC) and the normal control group (CON). The metabolic profiles of the five groups were clearly distinguished from each other. Furthermore, significant inter-metabolite correlations were extracted and used to reconstruct perturbed metabolic networks associated with the four pathological stages compared with the normal stage. Then, significantly altered metabolic pathways were identified by pathway analysis. Our results showed that oxidative stress-related metabolic pathways, choline phosphorylation and fatty acid degradation were continually disturbed during gastric carcinogenesis. Moreover, amino acid metabolism was perturbed dramatically in gastric dysplasia and GC. The GC stage showed more changed metabolite levels and more altered metabolic pathways. Two activated pathways (glycolysis; glycine, serine and threonine metabolism) substantially contributed to the metabolic alterations in GC. These results lay the basis for addressing the molecular mechanisms underlying gastric carcinogenesis and extend our understanding of GC progression.
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.
authors.forename: Jinping
authors.initials: J
authors.lastname: Gu
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Hu
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.|Pathology department, The Affiliated Chenggong Hospital, Xiamen University, Xiamen, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Shao
authors.affiliation: Pathology department, The Affiliated Chenggong Hospital, Xiamen University, Xiamen, P.R. China.
authors.forename: Tianhai
authors.initials: T
authors.lastname: Ji
authors.affiliation: Pathology department, The Affiliated Chenggong Hospital, Xiamen University, Xiamen, P.R. China.
authors.forename: Wensheng
authors.initials: W
authors.lastname: Yang
authors.affiliation: Department of Gastrointestinal Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, P.R. China.
authors.forename: Huiqin
authors.initials: H
authors.lastname: Zhuo
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.
authors.forename: Zeyu
authors.initials: Z
authors.lastname: Jin
authors.affiliation: State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, P.R. China.
authors.forename: Huiying
authors.initials: H
authors.lastname: Huang
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.
authors.forename: Jiacheng
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Physical Education, Xiamen University of Technology, Xiamen, P.R. China.
authors.forename: Caihua
authors.initials: C
authors.lastname: Huang
authors.affiliation: High-field NMR Research Center, MOE Key Laboratory of Spectrochemical Analysis & Instrumentation, Department of Chemical Biology, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, P.R. China.
authors.forename: Donghai
authors.initials: D
authors.lastname: Lin
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D002794:Choline / Q000378:metabolism; D004195:Disease Models, Animal; D005756:Gastritis / Q000378:metabolism*; D006019:Glycolysis; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D053858:Metabolic Networks and Pathways; D055432:Metabolomics; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar; D013274:Stomach Neoplasms / Q000378:metabolism*
chemical_list: D002794:Choline
keywords: NMR; gastric carcinogenesis; metabolic network; metabolic pathways; metabolomics