Oncotarget

Research Papers:

Metabolomic analysis reveals altered metabolic pathways in a rat model of gastric carcinogenesis

Jinping Gu, Xiaomin Hu, Wei Shao, Tianhai Ji, Wensheng Yang, Huiqin Zhuo, Zeyu Jin, Huiying Huang, Jiacheng Chen, Caihua Huang _ and Donghai Lin

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Oncotarget. 2016; 7:60053-60073. https://doi.org/10.18632/oncotarget.11049

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Abstract

Jinping Gu1, Xiaomin Hu1, Wei Shao1,3, Tianhai Ji3, Wensheng Yang3, Huiqin Zhuo4, Zeyu Jin1, Huiying Huang5, Jiacheng Chen1, Caihua Huang2, Donghai Lin1

1High-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

2Department of Physical Education, Xiamen University of Technology, Xiamen, P.R. China

3Department of Pathology, The Affiliated Chenggong Hospital, Xiamen University, Xiamen, P.R. China

4Department of Gastrointestinal Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, P.R. China

5State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, P.R. China

Correspondence to:

Caihua Huang, email: huangcaihua@xmut.edu.cn

Donghai Lin, email: dhlin@xmu.edu.cn

Keywords: gastric carcinogenesis, metabolic network, metabolic pathways, metabolomics, NMR

Received: April 03, 2016     Accepted: July 07, 2016     Published: August 04, 2016

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.


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