Cargando…

A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas

SIMPLE SUMMARY: Since the publication in 2016 of the WHO’s classification of primary brain tumors according to their histopathology but also their molecular status (IDH, 1p/19q codeletion), oligodendrogliomas defined by the presence of the 1p/19q codeletion have been clearly identified as having a b...

Descripción completa

Detalles Bibliográficos
Autores principales: Gilhodes, Julia, Meola, Adèle, Cabarrou, Bastien, Peyraga, Guillaume, Dehais, Caroline, Figarella-Branger, Dominique, Ducray, François, Maurage, Claude-Alain, Loussouarn, Delphine, Uro-Coste, Emmanuelle, Cohen-Jonathan Moyal, Elizabeth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296584/
https://www.ncbi.nlm.nih.gov/pubmed/37370678
http://dx.doi.org/10.3390/cancers15123067
_version_ 1785063684802871296
author Gilhodes, Julia
Meola, Adèle
Cabarrou, Bastien
Peyraga, Guillaume
Dehais, Caroline
Figarella-Branger, Dominique
Ducray, François
Maurage, Claude-Alain
Loussouarn, Delphine
Uro-Coste, Emmanuelle
Cohen-Jonathan Moyal, Elizabeth
author_facet Gilhodes, Julia
Meola, Adèle
Cabarrou, Bastien
Peyraga, Guillaume
Dehais, Caroline
Figarella-Branger, Dominique
Ducray, François
Maurage, Claude-Alain
Loussouarn, Delphine
Uro-Coste, Emmanuelle
Cohen-Jonathan Moyal, Elizabeth
author_sort Gilhodes, Julia
collection PubMed
description SIMPLE SUMMARY: Since the publication in 2016 of the WHO’s classification of primary brain tumors according to their histopathology but also their molecular status (IDH, 1p/19q codeletion), oligodendrogliomas defined by the presence of the 1p/19q codeletion have been clearly identified as having a better prognosis. However, the response to treatment of 1p/19q codeleted gliomas remains heterogeneous. Very few studies have investigated the genetic profiles of these tumors, particularly with regard to their response to treatment (radiotherapy and chemotherapy). Our analyses revealed a gene signature composed of eight genes involved in metabolism, immunity, and extracellular matrix organization pathways that were associated with a poor response to treatment for 1p/19q codeleted tumors. This signature could be used in the future to identify patients who need more intensive treatment, potentially with inhibitors of these pathways. ABSTRACT: Background. IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with oligodendrogliomas, all treated with radiotherapy +/− chemotherapy. Methods. We extracted total RNA from frozen tumor samples and investigated enriched pathways using KEGG and Reactome databases. We applied a stability selection approach based on subsampling combined with the lasso-pcvl algorithm to identify genes associated with progression-free survival and calculate a risk score. Results. We included 68 patients with oligodendrogliomas treated with radiotherapy +/− chemotherapy. After filtering, 1697 genes were obtained, including 134 associated with progression-free survival: 35 with a better prognosis and 99 with a poorer one. Eight genes (ST3GAL6, QPCT, NQO1, EPHX1, CST3, S100A8, CHI3L1, and OSBPL3) whose risk score remained statistically significant after adjustment for prognostic factors in multivariate analysis were selected in more than 60% of cases were associated with shorter progression-free survival. Conclusions. We found an eight-gene signature associated with a higher risk of rapid relapse after treatment in patients with oligodendrogliomas. This finding could help clinicians identify patients who need more intensive treatment.
format Online
Article
Text
id pubmed-10296584
institution National Center for Biotechnology Information
language English
publishDate 2023
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-102965842023-06-28 A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas Gilhodes, Julia Meola, Adèle Cabarrou, Bastien Peyraga, Guillaume Dehais, Caroline Figarella-Branger, Dominique Ducray, François Maurage, Claude-Alain Loussouarn, Delphine Uro-Coste, Emmanuelle Cohen-Jonathan Moyal, Elizabeth Cancers (Basel) Article SIMPLE SUMMARY: Since the publication in 2016 of the WHO’s classification of primary brain tumors according to their histopathology but also their molecular status (IDH, 1p/19q codeletion), oligodendrogliomas defined by the presence of the 1p/19q codeletion have been clearly identified as having a better prognosis. However, the response to treatment of 1p/19q codeleted gliomas remains heterogeneous. Very few studies have investigated the genetic profiles of these tumors, particularly with regard to their response to treatment (radiotherapy and chemotherapy). Our analyses revealed a gene signature composed of eight genes involved in metabolism, immunity, and extracellular matrix organization pathways that were associated with a poor response to treatment for 1p/19q codeleted tumors. This signature could be used in the future to identify patients who need more intensive treatment, potentially with inhibitors of these pathways. ABSTRACT: Background. IDH mutant and 1p/19q codeleted oligodendrogliomas are the gliomas associated with the best prognosis. However, despite their sensitivity to treatment, patient survival remains heterogeneous. We aimed to identify gene expressions associated with response to treatment from a national cohort of patients with oligodendrogliomas, all treated with radiotherapy +/− chemotherapy. Methods. We extracted total RNA from frozen tumor samples and investigated enriched pathways using KEGG and Reactome databases. We applied a stability selection approach based on subsampling combined with the lasso-pcvl algorithm to identify genes associated with progression-free survival and calculate a risk score. Results. We included 68 patients with oligodendrogliomas treated with radiotherapy +/− chemotherapy. After filtering, 1697 genes were obtained, including 134 associated with progression-free survival: 35 with a better prognosis and 99 with a poorer one. Eight genes (ST3GAL6, QPCT, NQO1, EPHX1, CST3, S100A8, CHI3L1, and OSBPL3) whose risk score remained statistically significant after adjustment for prognostic factors in multivariate analysis were selected in more than 60% of cases were associated with shorter progression-free survival. Conclusions. We found an eight-gene signature associated with a higher risk of rapid relapse after treatment in patients with oligodendrogliomas. This finding could help clinicians identify patients who need more intensive treatment. MDPI 2023-06-06 /pmc/articles/PMC10296584/ /pubmed/37370678 http://dx.doi.org/10.3390/cancers15123067 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gilhodes, Julia
Meola, Adèle
Cabarrou, Bastien
Peyraga, Guillaume
Dehais, Caroline
Figarella-Branger, Dominique
Ducray, François
Maurage, Claude-Alain
Loussouarn, Delphine
Uro-Coste, Emmanuelle
Cohen-Jonathan Moyal, Elizabeth
A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title_full A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title_fullStr A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title_full_unstemmed A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title_short A Multigene Signature Associated with Progression-Free Survival after Treatment for IDH Mutant and 1p/19q Codeleted Oligodendrogliomas
title_sort multigene signature associated with progression-free survival after treatment for idh mutant and 1p/19q codeleted oligodendrogliomas
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10296584/
https://www.ncbi.nlm.nih.gov/pubmed/37370678
http://dx.doi.org/10.3390/cancers15123067
work_keys_str_mv AT gilhodesjulia amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT meolaadele amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT cabarroubastien amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT peyragaguillaume amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT dehaiscaroline amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT figarellabrangerdominique amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT ducrayfrancois amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT maurageclaudealain amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT loussouarndelphine amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT urocosteemmanuelle amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT cohenjonathanmoyalelizabeth amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT amultigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT gilhodesjulia multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT meolaadele multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT cabarroubastien multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT peyragaguillaume multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT dehaiscaroline multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT figarellabrangerdominique multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT ducrayfrancois multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT maurageclaudealain multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT loussouarndelphine multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT urocosteemmanuelle multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT cohenjonathanmoyalelizabeth multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas
AT multigenesignatureassociatedwithprogressionfreesurvivalaftertreatmentforidhmutantand1p19qcodeletedoligodendrogliomas