{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:54:40Z","timestamp":1785898480234,"version":"3.56.0"},"reference-count":66,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T00:00:00Z","timestamp":1701302400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100004319","name":"Pfizer","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100004319","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Spanish National Taskforce on Neuroendocrine Tumors"},{"name":"Ministry of Science, Innovation and Universities of Spain"},{"DOI":"10.13039\/501100002924","name":"FEDER","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002924","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012818","name":"Autonomous Community of Madrid","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100012818","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAM"},{"name":"Progama de Empleo Juvenil"},{"DOI":"10.13039\/501100000780","name":"European Union","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"CAM"},{"name":"CAM"},{"DOI":"10.13039\/501100002704","name":"AECC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002704","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>Metabolic profiling is a valuable tool to characterize tumor biology but remains largely unexplored in neuroendocrine tumors (NETs). Our aim was to comprehensively assess the metabolomic profile of NETs and identify novel prognostic biomarkers and dysregulated molecular pathways.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design and Methods<\/jats:title>\n                  <jats:p>Multiplatform untargeted metabolomic profiling (GC-MS, CE-MS, and LC-MS) was performed in plasma from 77 patients with G1-2 extra-pancreatic NETs enrolled in the AXINET trial (NCT01744249) (study cohort) and from 68 non-cancer individuals (control). The prognostic value of each differential metabolite (n = 155) in NET patients (P &amp;lt; .05) was analyzed by univariate and multivariate analyses adjusted for multiple testing and other confounding factors. Related pathways were explored by Metabolite Set Enrichment Analysis (MSEA) and Metabolite Pathway Analysis (MPA).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Thirty-four metabolites were significantly associated with progression-free survival (PFS) (n = 16) and\/or overall survival (OS) (n = 27). Thirteen metabolites remained significant independent prognostic factors in multivariate analysis, 3 of them with a significant impact on both PFS and OS. Unsupervised clustering of these 3 metabolites stratified patients in 3 distinct prognostic groups (1-year PFS of 71.1%, 47.7%, and 15.4% (P = .012); 5-year OS of 69.7%, 32.5%, and 27.7% (P = .003), respectively). The MSEA and MPA of the 13-metablolite signature identified methionine, porphyrin, and tryptophan metabolisms as the 3 most relevant dysregulated pathways associated with the prognosis of NETs.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>We identified a metabolomic signature that improves prognostic stratification of NET patients beyond classical prognostic factors for clinical decisions. The enriched metabolic pathways identified reveal novel tumor vulnerabilities that may foster the development of new therapeutic strategies for these patients.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/ejendo\/lvad160","type":"journal-article","created":{"date-parts":[[2023,11,30]],"date-time":"2023-11-30T22:00:06Z","timestamp":1701381606000},"page":"62-74","source":"Crossref","is-referenced-by-count":9,"title":["Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival"],"prefix":"10.1093","volume":"190","author":[{"given":"Anna","family":"La Salvia","sequence":"first","affiliation":[{"name":"Center of Experimental Oncology, Gastrointestinal and Neuroendrocrine Tumors Research Group, Research Institute Hospital 12 de Octubre (imas12) , 28041 Madrid , Spain"},{"name":"Oncology Department, Hospital Universitario 12 de Octubre , 28041 Madrid , Spain"},{"name":"National Center for Drug Research and Evaluation, National Institute of Health (ISS) , 00161 Rome , Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Lens-Pardo","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology, Gastrointestinal and Neuroendrocrine Tumors Research Group, Research Institute Hospital 12 de Octubre (imas12) , 28041 Madrid , Spain"},{"name":"Spanish National Cancer Research Center (CNIO) , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angel","family":"L\u00f3pez-L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Facultad de Farmacia, Centre for Metabolomics and Bioanalysis (CEMBIO), Universidad San Pablo-CEU, CEU Universities , Urbanizaci\u00f3n Montepr\u00edncipe, Boadilla del Monte , 28925 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos","family":"Carretero-Puche","sequence":"additional","affiliation":[{"name":"Center of Experimental Oncology, Gastrointestinal and Neuroendrocrine Tumors Research Group, Research Institute Hospital 12 de Octubre (imas12) , 28041 Madrid , Spain"},{"name":"Spanish National Cancer Research Center (CNIO) , 28029 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaume","family":"Capdevila","sequence":"additional","affiliation":[{"name":"Vall Hebron University Hospital and Vall Hebron Institute of Oncology (VHIO) , 08035 Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Benavent","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Virgen del Roc\u00edo, Instituto de Biomedicina de Sevilla (IBIS) , 41013 Seville , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Jim\u00e9nez-Fonseca","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Hospital Universitario Central de Asturias, ISPA , 33011 Oviedo , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Castellano","sequence":"additional","affiliation":[{"name":"Oncology Department, Hospital Universitario 12 de Octubre , 28041 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa","family":"Alonso","sequence":"additional","affiliation":[{"name":"Medical Oncology, Hospital Universitario Ram\u00f3n y Cajal , 28034 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandre","family":"Teule","sequence":"additional","affiliation":[{"name":"Institut Catal\u00e0 d'Oncologia (ICO)-Institut d'Investigaci\u00f3 Biom\u00e8dica de Bellvitge (IDIBELL), 08908 L'Hospitalet del Llobregat , Barcelona , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana","family":"Custodio","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Hospital Universitario La Paz, CIBERONC CB16\/12\/00398 , 28046 Madrid , Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Tafuto","sequence":"additional","affiliation":[{"name":"Sarcomas and Rare Tumours Unit, Istituto Nazionale Tumori, IRCCS Fondazione G. 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