Both p53 codon 72 Arg/Arg and pro/Arg genotypes in glioblastoma multiforme are associated with a better prognosis in bevacizumab treatment.
Angiogenesis Inhibitors
/ therapeutic use
Antineoplastic Agents, Immunological
/ therapeutic use
Arginine
/ genetics
Bevacizumab
/ therapeutic use
Brain Neoplasms
/ drug therapy
Codon
Female
Gene Amplification
Genes, p53
Genotype
Glioblastoma
/ drug therapy
Humans
Male
Middle Aged
Neoplasm Recurrence, Local
/ drug therapy
Pilot Projects
Polymorphism, Genetic
Prognosis
Proline
/ genetics
Retrospective Studies
Sequence Analysis, DNA
Taiwan
Treatment Outcome
Bevacizumab
Codon 72
Glioblastoma multiforme
Polymorphism
SNP
p53
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
29 Jul 2020
29 Jul 2020
Historique:
received:
06
11
2019
accepted:
23
07
2020
entrez:
31
7
2020
pubmed:
31
7
2020
medline:
7
2
2021
Statut:
epublish
Résumé
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. 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. The 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. We 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. This 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.
Sections du résumé
BACKGROUND
BACKGROUND
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. 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.
METHODS
METHODS
The 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.
RESULTS
RESULTS
We 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.
CONCLUSIONS
CONCLUSIONS
This 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.
Identifiants
pubmed: 32727419
doi: 10.1186/s12885-020-07210-8
pii: 10.1186/s12885-020-07210-8
pmc: PMC7391574
doi:
Substances chimiques
Angiogenesis Inhibitors
0
Antineoplastic Agents, Immunological
0
Codon
0
Bevacizumab
2S9ZZM9Q9V
Arginine
94ZLA3W45F
Proline
9DLQ4CIU6V
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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