<i>TP53</i> 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 <i>tumour protein 53</i> (<i>TP53</i>) is prevalent in astrocytoma, the prognostic effects of <i>TP53</i> mutation are unclear....
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| Autores principales: | , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
MDPI AG
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/45f3e58e52dd470a99b0524811570245 |
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| Sumario: | 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. |
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