دورية أكاديمية
Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival
| العنوان: | Metabolomic profile of neuroendocrine tumors identifies methionine, porphyrin, and tryptophan metabolisms as key dysregulated pathways associated with patient survival |
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| المؤلفون: | LA SALVIA, ANNA, Lens-Pardo, Alberto, López-López, Angel, Carretero-Puche, Carlos, Benavent, Marta, Capdevila Castillon, Jaume |
| المساهمون: | Institut Català de la Salut, La Salvia A Center of Experimental Oncology, Gastrointestinal and Neuroendrocrine Tumors Research Group, Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain. Oncology Department, Hospital Universitario 12 de Octubre, Madrid, Spain. National Center for Drug Research and Evaluation, National Institute of Health (ISS), Rome, Italy. Lens-Pardo A, Carretero-Puche C Center of Experimental Oncology, Gastrointestinal and Neuroendrocrine Tumors Research Group, Research Institute Hospital 12 de Octubre (imas12), Madrid, Spain. Spanish National Cancer Research Center (CNIO), Madrid, Spain. López-López A Department of Chemistry and Biochemistry, Facultad de Farmacia, Centre for Metabolomics and Bioanalysis (CEMBIO), Universidad San Pablo-CEU, CEU Universities, Urbanización Montepríncipe, Boadilla del Monte, Madrid, Spain. Capdevila J Vall d’Hebron Hospital Universitari, Barcelona, Spain. Vall Hebron Institute of Oncology (VHIO), Barcelona, Spain. Benavent M Medical Oncology Department, Hospital Virgen del Rocío, Instituto de Biomedicina de Sevilla (IBIS), Seville, Spain, Vall d'Hebron Barcelona Hospital Campus |
| المصدر: | Scientia |
| بيانات النشر: | Oxford University Press |
| سنة النشر: | 2024 |
| مصطلحات موضوعية: | Metabolòmica, Marcadors bioquímics, Tumors neuroendocrins, DISEASES::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Germ Cell and Embryonal::Neuroectodermal Tumors::Neuroendocrine Tumors, DISCIPLINES AND OCCUPATIONS::Natural Science Disciplines::Biological Science Disciplines::Biochemistry::Metabolomics, CHEMICALS AND DRUGS::Biological Factors::Biomarkers, ENFERMEDADES::neoplasias::neoplasias por tipo histológico::neoplasias de células germinales y embrionarias::tumores neuroectodérmicos::tumores neuroendocrinos, DISCIPLINAS Y OCUPACIONES::disciplinas de las ciencias naturales::disciplinas de las ciencias biológicas::bioquímica::metabolómica, COMPUESTOS QUÍMICOS Y DROGAS::factores biológicos::biomarcadores |
| الوصف: | Metabolomics; Neuroendocrine tumors; Plasma metabolites ; Metabolòmica; Tumors neuroendocrins; Metabòlits plasmàtics ; Metabolómica; Tumores neuroendocrinos; Metabolitos plasmáticos ; Objective 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. Design and Methods 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 < .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). Results 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. Conclusions 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 ... |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 0804-4643 38033321 |
| العلاقة: | European Journal of Endocrinology;190(1); https://doi.org/10.1093/ejendo/lvad160Test; La Salvia A, Lens-Pardo A, López-López A, Carretero-Puche C, Capdevila J, Benavent M, et al. Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival. Eur J Endocrinol. 2024 Jan;190(1):62–74.; https://hdl.handle.net/11351/10892Test; 001138735800002 |
| DOI: | 10.1093/ejendo/lvad160 |
| الإتاحة: | https://doi.org/10.1093/ejendo/lvad160Test https://hdl.handle.net/11351/10892Test |
| حقوق: | Attribution-NonCommercial 4.0 International ; http://creativecommons.org/licenses/by-nc/4.0Test/ ; info:eu-repo/semantics/openAccess |
| رقم الانضمام: | edsbas.BC0F5C84 |
| قاعدة البيانات: | BASE |
| تدمد: | 08044643 38033321 |
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| DOI: | 10.1093/ejendo/lvad160 |