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.
METHODS: In this retrospective study, we sequenced TP53 exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings.
RESULTS: In astrocytoma, mutations in TP53 codon 273 were associated with a significantly increased OS compared to the TP53 wild-type (HR (95% CI): 0.169 (0.036-0.766), p = 0.021). Public datasets confirmed these findings. TP53 codon 273 mutant astrocytomas were significantly more chemosensitive than TP53 wild-type astrocytomas (HR (95% CI): 0.344 (0.13-0.88), p = 0.0148). Post-chemotherapy, a significant correlation between TP53 and YAP1 mRNA was found (p = 0.01). In O (6)-methylguanine methyltransferase (MGMT) unmethylated chemotherapy-treated astrocytoma, both TP53 codon 273 and YAP1 mRNA were significant prognostic markers. In oligodendroglioma, TP53 mutations were associated with significantly decreased OS.
CONCLUSIONS: Based on these findings, we propose that certain TP53 mutant astrocytomas are chemosensitive through the involvement of YAP1, and we outline a potential mechanism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:13 |
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| Enthalten in: |
Cancers - 13(2021), 21 vom: 26. Okt. |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Noor, Humaira [VerfasserIn] |
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| Links: |
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| Themen: |
Chemosensitivity |
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| Anmerkungen: |
Date Revised 04.04.2024 published: Electronic Citation Status PubMed-not-MEDLINE |
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| doi: |
10.3390/cancers13215362 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM333093518 |
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| 520 | |a 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 | ||
| 520 | |a METHODS: In this retrospective study, we sequenced TP53 exons 1 to 10 in a cohort of 102 lower-grade glioma (LGG) subtypes and determined the prognostic effects of TP53 mutation in astrocytoma and oligodendroglioma. Publicly available datasets were analysed to confirm the findings | ||
| 520 | |a RESULTS: In astrocytoma, mutations in TP53 codon 273 were associated with a significantly increased OS compared to the TP53 wild-type (HR (95% CI): 0.169 (0.036-0.766), p = 0.021). Public datasets confirmed these findings. TP53 codon 273 mutant astrocytomas were significantly more chemosensitive than TP53 wild-type astrocytomas (HR (95% CI): 0.344 (0.13-0.88), p = 0.0148). Post-chemotherapy, a significant correlation between TP53 and YAP1 mRNA was found (p = 0.01). In O (6)-methylguanine methyltransferase (MGMT) unmethylated chemotherapy-treated astrocytoma, both TP53 codon 273 and YAP1 mRNA were significant prognostic markers. In oligodendroglioma, TP53 mutations were associated with significantly decreased OS | ||
| 520 | |a CONCLUSIONS: Based on these findings, we propose that certain TP53 mutant astrocytomas are chemosensitive through the involvement of YAP1, and we outline a potential mechanism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a MGMT methylation | |
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| 700 | 1 | |a Briggs, Nancy E |e verfasserin |4 aut | |
| 700 | 1 | |a McDonald, Kerrie L |e verfasserin |4 aut | |
| 700 | 1 | |a Holst, Jeff |e verfasserin |4 aut | |
| 700 | 1 | |a Vittorio, Orazio |e verfasserin |4 aut | |
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