Both p53 codon 72 Arg/Arg and pro/Arg genotypes in glioblastoma multiforme are associated with a better prognosis in bevacizumab treatment

Chiung-Chyi Shen,Tsuo-Fei Mao,Wen-Yu Cheng,Chung-Hsin Lee,Jun-Peng Chen,Yea-Jiuen Liang,Shou-Ren Chen,Ming-Tsang Chiao,Bai-Shuan Liu,Xue-Jun Dai,Wan-Yu Hsieh,Guo-Shi Lin

doi:10.1186/s12885-020-07210-8

Abstract

BackgroundIt has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. However, an effective biomarker for predicting the prognosis of bevacizumab treatment has yet to be identified. This study, therefore, aimed to retrospectively analyze the polymorphisms of p53 codon 72 and the clinical characteristics of GBM specimens from Taiwanese patients.MethodsThe polymorphisms of p53 codon 72 in 99 patients with GBM treated at Taichung Veterans General Hospital in Taiwan from 2007 to 2017 were analyzed using direct DNA sequencing and PCR-RFLP analysis.ResultsWe found that among these GBM patients, the distribution of codon 72 polymorphisms was 28.3% for proline homozygotes (Pro/Pro), 38.4% for arginine homozygotes (Arg/Arg), and 33.3% for proline/arginine heterozygotes (Pro/Arg). Although the polymorphisms of p53 codon 72 were not directly associated with the overall survival of GBM, both the Arg/Arg and Arg/Pro genotypes were associated with significant benefits in terms of overall survival in patients treated with CCRT plus bevacizumab compared to patients treated with CCRT alone.ConclusionsThis pilot study suggests that both the Arg/Arg and Arg/Pro genotypes of p53 codon 72 polymorphism may have value as independent prognostic or predictive parameters for bevacizumab treatment response and failure. Relatedly, the results of the study further demonstrate the utility of stratifying GBM patients according to bevacizumab sensitivity.

Highlights

It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers
In conducting the DNA sequencing of dozens of glioblastoma multiforme (GBM) specimens and cell lines, we found 6 abnormal single nucleotide polymorphisms (SNPs) or losses of nucleotides, and we gave each of them a sequence coding number (1–6)
In this study, we only investigated the polymorphisms of p53 codon 72 and the tumor spectrums of Taiwanese patients with GBM, ignoring the question of whether or not the p53 gene had a mutation in any given case

Summary

Introduction

It has previously been shown that bevacizumab, when added to chemotherapy, improved overall survival in several cancers. In glioblastoma multiforme (GBM), bevacizumab increased progression-free survival and it is widely used for tumor recurrence, though it has failed to improve overall survival (OS) in controlled trials. In addition to mutations that inactivate the functions of p53, many single nucleotide polymorphisms (SNPs) have been identified in the p53 gene that influence the molecular function of the p53 protein as the guardian of the genome [4]. The p53 mutation database of the International Agency for Research on Cancer (IARC) lists 29 common polymorphisms in the non-coding region of TP53 [5]. Among these SNPs of the p53 gene, one well-known SNP that occurs on codon 72, the Arg72Pro polymorphism (rs1042522), is common. While many case-control studies have investigated the association between p53 codon 72 Arg/ Pro polymorphisms and glioma risk, those studies have provided inconsistent findings

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