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...
Autores principales: | , , , , , , , , , , |
---|---|
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 |