Tp53 mutation is a prognostic factor in lower grade glioma and may influence chemotherapy efficacy

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 mech-anism. Thus, TP53 mutations may be key drivers of astrocytoma therapeutic efficacy and influence survival outcomes.