English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Plus monthly

Global: Zendy Tools annual

Global: Zendy Tools monthly

Global: Zendy Free Plan

Simple Summary  Molecular biomarkers are utilised for the development of targeted therapy and diagnostic or prognostic tools and in strategising therapeutic approaches as they may have an effect in drug response. In lower-grade glioma (LGG), there are currently no established biomarkers that are associated with chemosensitivity. Here, we identified  tumour protein 53 (TP53)  hotspot mutations in  TP53  codon 273 in 33% (17/51) of astrocytoma tissues and retrospectively found that these tumours were associated with significantly improved clinical outcomes when treated with chemotherapy. We used publicly available datasets to successfully confirm these findings. A potential mechanism of this chemosensitivity was explored in this study.  TP53  codon 273 mutations can, thus, potentially be an indicator of chemotherapeutic efficacy in astrocytoma, and it may be useful in making astrocytoma treatment decisions.    Abstract  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.

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