{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:14:00Z","timestamp":1787944440813,"version":"build-2784847793"},"reference-count":48,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2020,6,4]],"date-time":"2020-06-04T00:00:00Z","timestamp":1591228800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004731","name":"Natural Science Foundation of Zhejiang Province","doi-asserted-by":"publisher","award":["LQ18B050003"],"award-info":[{"award-number":["LQ18B050003"]}],"id":[{"id":"10.13039\/501100004731","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["31971357"],"award-info":[{"award-number":["31971357"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011002","name":"National Natural Science Foundation of China-Yunnan Joint Fund","doi-asserted-by":"publisher","award":["81574080"],"award-info":[{"award-number":["81574080"]}],"id":[{"id":"10.13039\/501100011002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gastric 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\u2010based 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\u2010grade gastric dysplasia, high\u2010grade 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.<\/jats:p>","DOI":"10.1111\/cas.14443","type":"journal-article","created":{"date-parts":[[2020,5,5]],"date-time":"2020-05-05T20:18:19Z","timestamp":1588709899000},"page":"3195-3209","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":33,"title":["Nuclear magnetic resonance\u2010based tissue metabolomic analysis clarifies molecular mechanisms of gastric carcinogenesis"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-3624","authenticated-orcid":false,"given":"Jinping","family":"Gu","sequence":"first","affiliation":[{"name":"College of Chemistry and Chemical Engineering Key Laboratory for Chemical Biology of Fujian Province High\u2010field NMR Center Xiamen University Xiamen China"},{"name":"College of Pharmaceutical Sciences Key Laboratory for Green Pharmaceutical Technologies and Related Equipment of Ministry of Education Zhejiang University of Technology Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5134-0169","authenticated-orcid":false,"given":"Caihua","family":"Huang","sequence":"additional","affiliation":[{"name":"Research and Communication Center of Exercise and Health Xiamen University of Technology Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5921-1051","authenticated-orcid":false,"given":"Xiaomin","family":"Hu","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Key Laboratory for Chemical Biology of Fujian Province High\u2010field NMR Center Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9499-5560","authenticated-orcid":false,"given":"Jinmei","family":"Xia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Marine Biogenetic Resources Third Institute of Oceanography State Oceanic Administration Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9555-3091","authenticated-orcid":false,"given":"Wei","family":"Shao","sequence":"additional","affiliation":[{"name":"Affiliated Cardiovascular Hospital of Xiamen University Medical College of Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2318-2033","authenticated-orcid":false,"given":"Donghai","family":"Lin","sequence":"additional","affiliation":[{"name":"College of Chemistry and Chemical Engineering Key Laboratory for Chemical Biology of Fujian Province High\u2010field NMR Center Xiamen University Xiamen China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,4]]},"reference":[{"key":"e_1_2_7_2_1","series-title":"World Cancer Reports","volume-title":"World Cancer Report 2014","author":"Stewart BW","year":"2015"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10120-003-0265-0"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature06734"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc2827"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2011.02.013"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i36.12874"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11049"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.2217\/14622416.7.7.1095"},{"key":"e_1_2_7_10_1","first-page":"431","article-title":"Tissue metabolomic fingerprinting reveals 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