{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T16:33:19Z","timestamp":1793464399757,"version":"4.5.0"},"reference-count":26,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R35-CA-220449"],"award-info":[{"award-number":["R35-CA-220449"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p\/>\n               <jats:sec>\n                  <jats:title>OBJECTIVES<\/jats:title>\n                  <jats:p>A study of tumour metabolic reprogramming has revealed disease biomarkers and avenues for therapeutic intervention. Metabolic reprogramming in thymoma is currently understudied and largely unknown. This study utilized metabolomics and isotope tracing with 13C-glucose to metabolically investigate thymomas, adjacent thymic tissue and benign thymic lesions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>METHODS<\/jats:title>\n                  <jats:p>From 2017 to 2021, 20 patients with a suspected thymoma were recruited to this prospective Institutional Review Board approved clinical trial. At the time of surgery, 11 patients were infused with 13C-glucose, a stable, non-radioactive tracer which reports the flow of carbon through metabolic pathways. Samples were analysed by mass spectrometry to measure the abundance of &amp;gt;200 metabolites.13C enrichment was measured in patients who received 13C-glucose infusions.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>RESULTS<\/jats:title>\n                  <jats:p>Histological analysis showed that 9 patients had thymomas of diverse subtypes and 11 patients had benign cysts. In our metabolomic analysis, thymomas could be distinguished from both adjacent thymus tissue and benign lesions by metabolite abundances. Metabolites in pyrimidine biosynthesis and glycerophospholipid metabolism were differentially expressed across these tissues.13C-glucose infusions revealed differential labelling patterns in thymoma compared to benign cysts and normal thymus tissue. The lactate\/3PG labelling ratio, a metabolic marker in aggressive lung tumours correlated with lactate uptake, was increased in thymomas (1.579) compared to normal thymus (0.945) and benign masses (0.807) (thymic tissue versus tumour P\u2009=\u20090.021, tumour versus benign P\u2009=\u20090.013).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>CONCLUSIONS<\/jats:title>\n                  <jats:p>We report metabolic biomarkers, including differential 13C labelling of metabolites from central metabolism, that distinguish thymomas from benign tissues. Altered glucose and lactate metabolism warrant further investigation and may provide novel therapeutic targets for thymoma.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejcts\/ezad394","type":"journal-article","created":{"date-parts":[[2023,11,25]],"date-time":"2023-11-25T06:29:07Z","timestamp":1700893747000},"source":"Crossref","is-referenced-by-count":7,"title":["Metabolic signatures of thymomas: potential biomarkers and treatment targets"],"prefix":"10.1093","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7150-0270","authenticated-orcid":false,"given":"James W","family":"Miller","sequence":"first","affiliation":[{"name":"School of Medicine, University of Texas Southwestern Medical Center , Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brandon M","family":"Faubert","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Section of Hematology and Oncology, Department of Medicine, University of Chicago , Chicago, IL, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas P","family":"Mathews","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John K","family":"Waters","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph J","family":"DeBerardinis","sequence":"additional","affiliation":[{"name":"Children\u2019s Medical Center Research Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Eugene McDermott Center for Human Growth and Development, University of Texas Southwestern Medical Center, Dallas, TX, USA"},{"name":"Howard Hughes Medical Institute, University of Texas Southwestern Medical Center , Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kemp H","family":"Kernstine","sequence":"additional","affiliation":[{"name":"Department of Cardiovascular and Thoracic Surgery, University of Texas Southwestern Medical Center, Dallas, TX, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"2024022209091311300_ezad394-B1","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.ccell.2018.01.003","article-title":"The integrated genomic Landscape of thymic epithelial tumors","volume":"33","author":"Radovich","year":"2018","journal-title":"Cancer Cell"},{"key":"2024022209091311300_ezad394-B2","first-page":"173","article-title":"Thymic neoplasm: a rare disease with a complex clinical presentation","volume":"5","author":"Rashid","year":"2013","journal-title":"J Thorac Dis"},{"key":"2024022209091311300_ezad394-B3","doi-asserted-by":"crossref","first-page":"4516","DOI":"10.3390\/cancers13184516","article-title":"Evaluation of surgical therapy in advanced thymic tumors","volume":"13","author":"Markowiak","year":"2021","journal-title":"Cancers (Basel)"},{"key":"2024022209091311300_ezad394-B4","doi-asserted-by":"crossref","first-page":"878","DOI":"10.1016\/S0003-4975(03)00555-1","article-title":"Therapy for thymic epithelial tumors: a clinical study of 1,320 patients from Japan","volume":"76","author":"Kondo","year":"2003","journal-title":"Ann Thoracic Surg"},{"key":"2024022209091311300_ezad394-B5","doi-asserted-by":"crossref","first-page":"705","DOI":"10.21037\/jtd.2016.01.79","article-title":"Outcome of nonsurgical treatment for locally advanced thymic tumors","volume":"8","author":"Wang","year":"2016","journal-title":"J Thorac Dis"},{"key":"2024022209091311300_ezad394-B6","doi-asserted-by":"crossref","first-page":"819","DOI":"10.1016\/j.ejcts.2009.11.001","article-title":"Predictors of survival in patients with locally advanced thymoma and thymic carcinoma (Masaoka stages III and IVa)","volume":"37","author":"Cardillo","year":"2010","journal-title":"Eur J Cardiothorac Surg"},{"key":"2024022209091311300_ezad394-B7","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: the next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"2024022209091311300_ezad394-B8","doi-asserted-by":"crossref","first-page":"787","DOI":"10.1056\/NEJM194806032382301","article-title":"Temporary remissions in acute leukemia in children produced by folic acid antagonist, 4-aminopteroyl-glutamic acid","volume":"238","author":"Farber","year":"1948","journal-title":"N Engl J Med."},{"key":"2024022209091311300_ezad394-B9","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1158\/2159-8290.CD-16-1034","article-title":"AG-221, a first-in-class therapy targeting acute myeloid leukemia harboring oncogenic IDH2 mutations","volume":"7","author":"Yen","year":"2017","journal-title":"Cancer Discov"},{"key":"2024022209091311300_ezad394-B10","doi-asserted-by":"crossref","first-page":"1161","DOI":"10.1016\/j.chembiol.2017.08.028","article-title":"Targeting metabolism for cancer therapy","volume":"24","author":"Luengo","year":"2017","journal-title":"Cell Chem Biol"},{"key":"2024022209091311300_ezad394-B11","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.3390\/cancers14061564","article-title":"Metabolic profiling of thymic epithelial tumors hints to a strong Warburg effect, glutaminolysis and precarious redox homeostasis as potential therapeutic targets","volume":"14","author":"Alwahsh","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2024022209091311300_ezad394-B12","doi-asserted-by":"crossref","first-page":"S131","DOI":"10.1097\/JTO.0000000000000298","article-title":"State of the art of genetic alterations in thymic epithelial tumors","volume":"9","author":"Rajan","year":"2014","journal-title":"J Thorac Oncol"},{"key":"2024022209091311300_ezad394-B13","doi-asserted-by":"crossref","first-page":"6790","DOI":"10.1158\/1078-0432.CCR-09-0644","article-title":"Comprehensive genomic analysis reveals clinically relevant molecular distinctions between thymic carcinomas and thymomas","volume":"15","author":"Girard","year":"2009","journal-title":"Clin Cancer Res"},{"key":"2024022209091311300_ezad394-B14","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/ng.3016","article-title":"A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors","volume":"46","author":"Petrini","year":"2014","journal-title":"Nat Genet."},{"key":"2024022209091311300_ezad394-B15","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.cell.2015.12.034","article-title":"Metabolic heterogeneity in human lung tumors","volume":"164","author":"Hensley","year":"2016","journal-title":"Cell."},{"key":"2024022209091311300_ezad394-B16","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.cell.2017.09.019","article-title":"Lactate metabolism in human lung tumors","volume":"171","author":"Faubert","year":"2017","journal-title":"Cell"},{"key":"2024022209091311300_ezad394-B17","doi-asserted-by":"crossref","first-page":"6494","DOI":"10.1021\/acs.analchem.7b05382","article-title":"A novel lipidomics workflow for improved human plasma identification and quantification using RPLC-MSn methods and isotope dilution strategies","volume":"90","author":"Rampler","year":"2018","journal-title":"Anal Chem"},{"key":"2024022209091311300_ezad394-B18","doi-asserted-by":"crossref","first-page":"e1600200","DOI":"10.1126\/sciadv.1600200","article-title":"Fundamentals of cancer metabolism","volume":"2","author":"DeBerardinis","year":"2016","journal-title":"Sci Adv"},{"key":"2024022209091311300_ezad394-B19","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.cmet.2015.12.006","article-title":"The emerging hallmarks of cancer metabolism","volume":"23","author":"Pavlova","year":"2016","journal-title":"Cell Metab"},{"key":"2024022209091311300_ezad394-B20","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.ccr.2012.02.014","article-title":"Metabolic reprogramming: a cancer hallmark even Warburg did not anticipate","volume":"21","author":"Ward","year":"2012","journal-title":"Cancer Cell"},{"key":"2024022209091311300_ezad394-B21","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1002\/nbm.790","article-title":"Changes in phosphate metabolism in thymoma cells suggest mechanisms for resistance to dexamethasone-induced apoptosis. A 31P NMR spectroscopic study of cell extracts","volume":"15","author":"Lutz","year":"2002","journal-title":"NMR Biomed"},{"key":"2024022209091311300_ezad394-B22","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12916-016-0552-3","article-title":"Higher plasma levels of lysophosphatidylcholine 18:0 are related to a lower risk of common cancers in a prospective metabolomics study","volume":"14","author":"Kuhn","year":"2016","journal-title":"BMC Med"},{"key":"2024022209091311300_ezad394-B23","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.cmet.2019.06.014","article-title":"Oncogene amplification in growth factor signaling pathways renders cancers dependent on membrane lipid remodeling","volume":"30","author":"Bi","year":"2019","journal-title":"Cell Metab"},{"key":"2024022209091311300_ezad394-B24","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1097\/PPO.0000000000000104","article-title":"Alternative fuels for cancer cells","volume":"21","author":"Keenan","year":"2015","journal-title":"Cancer J"},{"key":"2024022209091311300_ezad394-B25","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41586-019-1847-2","article-title":"Metabolic heterogeneity confers differences in melanoma metastatic potential","volume":"577","author":"Tasdogan","year":"2020","journal-title":"Nature"},{"key":"2024022209091311300_ezad394-B26","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1148\/radiol.2019182391","article-title":"Hyperpolarized 13C MRI: state of the art and future directions","volume":"291","author":"Wang","year":"2019","journal-title":"Radiology"}],"container-title":["European Journal of Cardio-Thoracic Surgery"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/ejcts\/advance-article-pdf\/doi\/10.1093\/ejcts\/ezad394\/53842940\/ezad394.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/65\/2\/ezad394\/56737170\/ezad394.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/ejcts\/article-pdf\/65\/2\/ezad394\/56737170\/ezad394.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T18:13:42Z","timestamp":1708625622000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/ejcts\/article\/doi\/10.1093\/ejcts\/ezad394\/7451836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,27]]},"references-count":26,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/ejcts\/ezad394","relation":{},"ISSN":["1873-734X"],"issn-type":[{"value":"1873-734X","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2023,11,27]]},"article-number":"ezad394"}}