Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival

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 an...

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Autores: Salvia, Anna La, Lens Pardo, Alberto, López López, Angel, Carretero Puche, Carlos, Capdevila, Jaume, Benavent, Marta, Jiménez Fonseca, Paula, Castellano, Daniel, Alonso, Teresa, Teule, Alexandre, Custodio, Ana, Tafuto, Salvatore, Casta, Adelaida La, Spada, Francesca, Lopez Gonzalvez, Angeles, Gil Calderon, Beatriz, Espinosa Olarte, Paula, Barbas, Coral, Garcia Carbonero, Rocio, Soldevilla, Beatriz
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2023
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/207657
Acceso en línea:https://hdl.handle.net/2445/207657
Access Level:acceso abierto
Palabra clave:Triptòfan
Porfirines
Tryptophan
Porphyrins
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spelling Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survivalSalvia, Anna LaLens Pardo, AlbertoLópez López, AngelCarretero Puche, CarlosCapdevila, JaumeBenavent, MartaJiménez Fonseca, PaulaCastellano, DanielAlonso, TeresaTeule, AlexandreCustodio, AnaTafuto, SalvatoreCasta, Adelaida LaSpada, FrancescaLopez Gonzalvez, AngelesGil Calderon, BeatrizEspinosa Olarte, PaulaBarbas, CoralGarcia Carbonero, RocioSoldevilla, BeatrizTriptòfanPorfirinesTryptophanPorphyrinsObjective: 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 development of new therapeutic strategies for these patients.Oxford University Press (OUP)2024202420232024info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion13 p.application/pdfhttps://hdl.handle.net/2445/207657Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésReproducció del document publicat a: https://doi.org/10.1093/ejendo/lvad160European Journal of Endocrinology, 2023, vol. 190, num. 1, p. 62-74https://doi.org/10.1093/ejendo/lvad160cc by-nc (c) Salvia, Anna La et al., 2023http://creativecommons.org/licenses/by-nc/3.0/es/info:eu-repo/semantics/openAccessoai:recercat.cat:2445/2076572026-05-29T05:05:01Z
dc.title.none.fl_str_mv Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
title Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
spellingShingle Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
Salvia, Anna La
Triptòfan
Porfirines
Tryptophan
Porphyrins
title_short Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
title_full Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
title_fullStr Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
title_full_unstemmed Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
title_sort Metabolomic profile of neuroendocrine tumors (NETs) identifies methionine, porphyrin and tryptophan metabolism as key dysregulated pathways associated with patient survival
dc.creator.none.fl_str_mv Salvia, Anna La
Lens Pardo, Alberto
López López, Angel
Carretero Puche, Carlos
Capdevila, Jaume
Benavent, Marta
Jiménez Fonseca, Paula
Castellano, Daniel
Alonso, Teresa
Teule, Alexandre
Custodio, Ana
Tafuto, Salvatore
Casta, Adelaida La
Spada, Francesca
Lopez Gonzalvez, Angeles
Gil Calderon, Beatriz
Espinosa Olarte, Paula
Barbas, Coral
Garcia Carbonero, Rocio
Soldevilla, Beatriz
author Salvia, Anna La
author_facet Salvia, Anna La
Lens Pardo, Alberto
López López, Angel
Carretero Puche, Carlos
Capdevila, Jaume
Benavent, Marta
Jiménez Fonseca, Paula
Castellano, Daniel
Alonso, Teresa
Teule, Alexandre
Custodio, Ana
Tafuto, Salvatore
Casta, Adelaida La
Spada, Francesca
Lopez Gonzalvez, Angeles
Gil Calderon, Beatriz
Espinosa Olarte, Paula
Barbas, Coral
Garcia Carbonero, Rocio
Soldevilla, Beatriz
author_role author
author2 Lens Pardo, Alberto
López López, Angel
Carretero Puche, Carlos
Capdevila, Jaume
Benavent, Marta
Jiménez Fonseca, Paula
Castellano, Daniel
Alonso, Teresa
Teule, Alexandre
Custodio, Ana
Tafuto, Salvatore
Casta, Adelaida La
Spada, Francesca
Lopez Gonzalvez, Angeles
Gil Calderon, Beatriz
Espinosa Olarte, Paula
Barbas, Coral
Garcia Carbonero, Rocio
Soldevilla, Beatriz
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv Triptòfan
Porfirines
Tryptophan
Porphyrins
topic Triptòfan
Porfirines
Tryptophan
Porphyrins
description 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 development of new therapeutic strategies for these patients.
publishDate 2023
dc.date.none.fl_str_mv 2023
2024
2024
2024
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv https://hdl.handle.net/2445/207657
url https://hdl.handle.net/2445/207657
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Reproducció del document publicat a: https://doi.org/10.1093/ejendo/lvad160
European Journal of Endocrinology, 2023, vol. 190, num. 1, p. 62-74
https://doi.org/10.1093/ejendo/lvad160
dc.rights.none.fl_str_mv cc by-nc (c) Salvia, Anna La et al., 2023
http://creativecommons.org/licenses/by-nc/3.0/es/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv cc by-nc (c) Salvia, Anna La et al., 2023
http://creativecommons.org/licenses/by-nc/3.0/es/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv 13 p.
application/pdf
dc.publisher.none.fl_str_mv Oxford University Press (OUP)
publisher.none.fl_str_mv Oxford University Press (OUP)
dc.source.none.fl_str_mv Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))
reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
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score 15,81155

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