Search

This work was partially funded by Pfizer, Project G1808 from the Spanish National Taskforce on Neuroendocrine Tumors (GETNE), Ministry of Science, Innovation and Universities of Spain (MICINN) and FEDER funding (Ref. RTI2018-095166-B-I00) and Autonomous Community of Madrid (NOVELREN-CM. Ref: B2017/BMD3751). B.S. is funded by AECC (POSTDO46SOLD, Spain). A.L.-L. thanks CEU-International Doctoral School (CEINDO) for her fellowship. A.L.-P. is funded by CAM (PEJD-2019-PRE/BMD-17058, Progama de Empleo Juvenil (YEI), co-funded by European Union (ERDF/ESF, “Investing in your future”). C.C.-P. was partially funded by CAM (PEJD-2016-PRE/BMD-2666). B.R.-C. was partially funded by CAM (PEJD-2017-PRE/BMD-4981). ALS is funded by Instituto de Salud Carlos III (Contrato Rio Hortega). M.R.-M. is funded by AECC (CLSEN19003RIES)., Purpose: High-throughput “-omic” technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Methods: Plasma samples from 77 NETs and 68 controls were profiled by GC−MS, CE−MS and LC−MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. Results: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. Conclusions: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research., Unión Europea, Ministerio de Ciencia e Innovación (España), Comunidad de Madrid, Grupo Español de Tumores Neuroendocrinos y Endocrinos (GETNE), Asociación Española Contra el Cáncer (AECC), Instituto de Salud Carlos III, Pfizer, Depto. de Medicina, Fac. de Medicina, TRUE, pub