TP53 Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy

Background: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in tumour protein 53 (TP53) is prevalent in astrocytoma, the prognostic effects of TP53 mutation are unclear....

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Autores principales:	Humaira Noor, Nancy E. Briggs, Kerrie L. McDonald, Jeff Holst, Orazio Vittorio
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	<i>TP53</i> mutation low-grade glioma LGG <i>MGMT</i> methylation <i>YAP1</i> chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/45f3e58e52dd470a99b0524811570245
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spelling	oai:doaj.org-article:45f3e58e52dd470a99b05248115702452021-11-11T15:29:13Z<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy10.3390/cancers132153622072-6694https://doaj.org/article/45f3e58e52dd470a99b05248115702452021-10-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5362https://doaj.org/toc/2072-6694Background: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in <i>tumour protein 53</i> (<i>TP53</i>) is prevalent in astrocytoma, the prognostic effects of <i>TP53</i> mutation are unclear. Methods: In this retrospective study, we sequenced <i>TP53</i> exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of <i>TP53</i> mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings. Results: In astrocytoma, mutations in <i>TP53</i> codon 273 were associated with a significantly increased OS compared to the <i>TP53</i> wild-type (HR (95% CI): 0.169 (0.036–0.766), <i>p</i> = 0.021). Public datasets confirmed these findings. <i>TP53</i> codon 273 mutant astrocytomas were significantly more chemosensitive than <i>TP53</i> wild-type astrocytomas (HR (95% CI): 0.344 (0.13–0.88), <i>p</i> = 0.0148). Post-chemotherapy, a significant correlation between <i>TP53</i> and <i>YAP1</i> mRNA was found (<i>p</i> = 0.01). In <i>O (6)-methylguanine methyltransferase (MGMT)</i> unmethylated chemotherapy-treated astrocytoma, both <i>TP53</i> codon 273 and <i>YAP1</i> mRNA were significant prognostic markers. In oligodendroglioma, <i>TP53</i> mutations were associated with significantly decreased OS. Conclusions: Based on these findings, we propose that certain <i>TP53</i> mutant astrocytomas are chemosensitive through the involvement of <i>YAP1</i>, and we outline a potential mechanism. Thus, <i>TP53</i> mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.Humaira NoorNancy E. BriggsKerrie L. McDonaldJeff HolstOrazio VittorioMDPI AGarticle<i>TP53</i> mutationlow-grade gliomaLGG<i>MGMT</i> methylation<i>YAP1</i>chemosensitivityNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5362, p 5362 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	<i>TP53</i> mutation low-grade glioma LGG <i>MGMT</i> methylation <i>YAP1</i> chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	<i>TP53</i> mutation low-grade glioma LGG <i>MGMT</i> methylation <i>YAP1</i> chemosensitivity Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Humaira Noor Nancy E. Briggs Kerrie L. McDonald Jeff Holst Orazio Vittorio <i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
description	Background: Identification of prognostic biomarkers in cancers is a crucial step to improve overall survival (OS). Although mutations in <i>tumour protein 53</i> (<i>TP53</i>) is prevalent in astrocytoma, the prognostic effects of <i>TP53</i> mutation are unclear. Methods: In this retrospective study, we sequenced <i>TP53</i> exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of <i>TP53</i> mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings. Results: In astrocytoma, mutations in <i>TP53</i> codon 273 were associated with a significantly increased OS compared to the <i>TP53</i> wild-type (HR (95% CI): 0.169 (0.036–0.766), <i>p</i> = 0.021). Public datasets confirmed these findings. <i>TP53</i> codon 273 mutant astrocytomas were significantly more chemosensitive than <i>TP53</i> wild-type astrocytomas (HR (95% CI): 0.344 (0.13–0.88), <i>p</i> = 0.0148). Post-chemotherapy, a significant correlation between <i>TP53</i> and <i>YAP1</i> mRNA was found (<i>p</i> = 0.01). In <i>O (6)-methylguanine methyltransferase (MGMT)</i> unmethylated chemotherapy-treated astrocytoma, both <i>TP53</i> codon 273 and <i>YAP1</i> mRNA were significant prognostic markers. In oligodendroglioma, <i>TP53</i> mutations were associated with significantly decreased OS. Conclusions: Based on these findings, we propose that certain <i>TP53</i> mutant astrocytomas are chemosensitive through the involvement of <i>YAP1</i>, and we outline a potential mechanism. Thus, <i>TP53</i> mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.
format	article
author	Humaira Noor Nancy E. Briggs Kerrie L. McDonald Jeff Holst Orazio Vittorio
author_facet	Humaira Noor Nancy E. Briggs Kerrie L. McDonald Jeff Holst Orazio Vittorio
author_sort	Humaira Noor
title	<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
title_short	<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
title_full	<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
title_fullStr	<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
title_full_unstemmed	<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy
title_sort	<i>tp53</i> mutation is a prognostic factor in lower grade glioma and may influence chemotherapy efficacy
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/45f3e58e52dd470a99b0524811570245
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<i>TP53</i> Mutation Is a Prognostic Factor in Lower Grade Glioma and May Influence Chemotherapy Efficacy

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