Nuclear magnetic resonance‐based tissue metabolomic analysis clarifies molecular mechanisms of gastric carcinogenesis

Cancer Science - Tập 111 Số 9 - Trang 3195-3209 - 2020
Jinping Gu1,2, Caihua Huang3, Xiaomin Hu1, Jin‐Mei Xia4, Wei Shao5, Donghai Lin1
1College of Chemistry and Chemical Engineering, Key Laboratory for Chemical Biology of Fujian Province, High-field NMR Center, Xiamen University, Xiamen, China
2College of Pharmaceutical Sciences, Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education, Zhejiang University of Technology, Hangzhou, China
3Research and Communication Center of Exercise and Health, Xiamen University of Technology, Xiamen, China
4Key Laboratory of Marine Biogenetic Resources, Third Institute of Oceanography, State Oceanic Administration, Xiamen, China
5Affiliated Cardiovascular Hospital of Xiamen University, Medical College of Xiamen University, Xiamen, China

Tóm tắt

AbstractGastric cancer (GC) is one of the deadliest cancers worldwide, and the progression of gastric carcinogenesis (GCG) covers multiple complicated pathological stages. Molecular mechanisms of GCG are still unclear. Here, we undertook NMR‐based metabolomic analysis of aqueous metabolites extracted from gastric tissues in an established rat model of GCG. We showed that the metabolic profiles were clearly distinguished among 5 histologically classified groups: control, gastritis, low‐grade gastric dysplasia, high‐grade gastric dysplasia (HGD), and GC. Furthermore, we carried out metabolic pathway analysis based on identified significant metabolites and revealed significantly disturbed metabolic pathways closely associated with the 4 pathological stages, including oxidation stress, choline phosphorylation, amino acid metabolism, Krebs cycle, and glycolysis. Three metabolic pathways were continually disturbed during the progression of GCG, including taurine and hypotaurine metabolism, glutamine and glutamate metabolism, alanine, aspartate, and glutamate metabolism. Both the Krebs cycle and glycine, serine, and threonine metabolism were profoundly impaired in both the HGD and GC stages, potentially due to abnormal energy supply for tumor cell proliferation and growth. Furthermore, valine, leucine, and isoleucine biosynthesis and glycolysis were significantly disturbed in the GC stage for higher energy requirement of the rapid growth of tumor cells. Additionally, we identified potential gastric tissue biomarkers for metabolically discriminating the 4 pathological stages, which also showed good discriminant capabilities for their serum counterparts. This work sheds light on the molecular mechanisms of GCG and is of benefit to the exploration of potential biomarkers for clinically diagnosing and monitoring the progression of GCG.

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Cancer Science

Tập 111 Số 9

3195-3209

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