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Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma
BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzi...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332894/ https://www.ncbi.nlm.nih.gov/pubmed/35911637 http://dx.doi.org/10.1093/noajnl/vdac097 |
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author | Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Otsuji, Ryosuke Hamada, Taiji Matsuo, Kei Kirishima, Mari Hata, Nobuhiro Hanaya, Ryosuke Tanimoto, Akihide Yoshimoto, Koji |
author_facet | Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Otsuji, Ryosuke Hamada, Taiji Matsuo, Kei Kirishima, Mari Hata, Nobuhiro Hanaya, Ryosuke Tanimoto, Akihide Yoshimoto, Koji |
author_sort | Higa, Nayuta |
collection | PubMed |
description | BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM. METHODS: Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status. RESULTS: We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P < .001). CONCLUSIONS: Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM. |
format | Online Article Text |
id | pubmed-9332894 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-93328942022-07-29 Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Otsuji, Ryosuke Hamada, Taiji Matsuo, Kei Kirishima, Mari Hata, Nobuhiro Hanaya, Ryosuke Tanimoto, Akihide Yoshimoto, Koji Neurooncol Adv Basic and Translational Investigations BACKGROUND: Platelet-derived growth factor receptor alpha (PDGFRA) is the second most frequently mutated tyrosine kinase receptor in glioblastoma (GBM). However, the prognostic impact of PDGFRA amplification on GBM patients remains unclear. Herein, we evaluated this impact by retrospectively analyzing outcomes of patients with IDH wild-type GBM. METHODS: Using a custom-made oncopanel, we evaluated PDGFRA gain/amplification in 107 GBM samples harboring wild-type IDH, along with MGMT promoter (MGMTp) methylation status. RESULTS: We detected PDGFRA gain/amplification in 31 samples (29.0%). PDGFRA gain/amplification predicted poor prognosis (P = .003). Compared to unamplified PDGFRA, PDGFRA gain/amplification in GBM was associated with higher patient age (P = .031), higher Ki-67 score (P = .019), and lower extent of surgical resection (P = .033). Unmethylated MGMTp also predicted poor prognosis (P = .005). As PDGFRA gain/amplification and unmethylated MGMTp were independent factors for poor prognosis in multivariate analyses, we grouped GBM cases based on PDGFRA and MGMTp status: poor (PDGFRA gain/amplification and unmethylated MGMTp), intermediate (PDGFRA gain/amplification or unmethylated MGMTp), and good (PDGFRA intact and methylated MGMTp) prognosis. The Kaplan-Meier survival analysis indicated that these groups significantly correlated with the OS of GBM patients (P < .001). CONCLUSIONS: Here we report that PDGFRA gain/amplification is a predictor of poor prognosis in IDH wild-type GBM. Combining PDGFRA gain/amplification with MGMTp methylation status improves individual prognosis prediction in patients with IDH wild-type GBM. Oxford University Press 2022-06-21 /pmc/articles/PMC9332894/ /pubmed/35911637 http://dx.doi.org/10.1093/noajnl/vdac097 Text en © The Author(s) 2022. Published by Oxford University Press, the Society for Neuro-Oncology and the European Association of Neuro-Oncology. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Basic and Translational Investigations Higa, Nayuta Akahane, Toshiaki Yokoyama, Seiya Yonezawa, Hajime Uchida, Hiroyuki Takajo, Tomoko Otsuji, Ryosuke Hamada, Taiji Matsuo, Kei Kirishima, Mari Hata, Nobuhiro Hanaya, Ryosuke Tanimoto, Akihide Yoshimoto, Koji Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title | Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title_full | Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title_fullStr | Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title_full_unstemmed | Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title_short | Prognostic impact of PDGFRA gain/amplification and MGMT promoter methylation status in patients with IDH wild-type glioblastoma |
title_sort | prognostic impact of pdgfra gain/amplification and mgmt promoter methylation status in patients with idh wild-type glioblastoma |
topic | Basic and Translational Investigations |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9332894/ https://www.ncbi.nlm.nih.gov/pubmed/35911637 http://dx.doi.org/10.1093/noajnl/vdac097 |
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