Journal Article

Polymorphism at codon 31 of CDKN1A (p21) as a predictive factor for bevacizumab therapy in glioblastoma multiforme

Chiao, Ming-Tsang, Liang, Yea-Jiuen, Shen, Chiung-Chyi, Lin, Cheng-Hui, Chen, Jun-Peng, Yang, Yi-Chin, Cheng, Wen-Yu, Hsieh, Wan-Yu

2023

Overview

Glioblastoma (GBM), a prevalent and malignant brain tumor, poses a challenge in surgical resection due to its invasive nature within the brain parenchyma. CDKN1A (p21, Waf-1), a cyclin-dependent kinase inhibitor, plays a pivotal role in regulating cell growth arrest, terminal differentiation, and apoptosis. The existence of natural variants of CDKN1A has been associated with specific cancer types. In this retrospective study, our objective was to identify polymorphic variants of CDKN1A, specifically c.93C > A (codon 31 Ser31Arg), and investigate its potential impact within the scope of bevacizumab therapy for glioblastoma multiforme. This study involved a cohort of 139 unrelated adult Chinese GBM patients in Taiwan. Genomic DNA extracted from tumor samples was utilized for genotyping using the polymerase chain reaction (PCR) restriction fragment length polymorphism method (PCR–RFLP analysis). Through unconditional logistic regression analysis, odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were calculated. Our findings unveiled that among these GBM patients, the distribution of codon 31 polymorphisms was as follows: 23.02% were Serine homozygotes (Ser/Ser), 27.34% were Arginine homozygotes (Arg/Arg), and 49.64% were Serine/Arginine heterozygotes (Ser/Arg). While CDKN1A c.93C > A polymorphisms did not exhibit a direct association with overall survival in GBM patients, noteworthy survival benefits emerged among individuals with Arg/Arg and Arg/Ser genotypes who received combined concurrent chemoradiotherapy (CCRT) and bevacizumab treatment compared to those who underwent CCRT alone. Our findings indicate a significant involvement of the CDKN1A c.93C > A polymorphism in the development and onset of GBM, offering potential implications for the early prognostication of bevacizumab therapy outcomes.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Analysis / Apoptosis / Bevacizumab / Biomedical and Life Sciences / Biomedicine / Brain cancer / Brain tumors / Cancer / Cancer Research / Cancer therapies / Care and treatment / CDKN1A c.93C > A / Cell cycle / Cell differentiation / Chemoradiotherapy / Chemotherapy / Codon / Cyclin-dependent kinase / Cyclin-dependent kinase inhibitor p21 / Cyclin-dependent kinases / Development and progression / FDA approval / Gene polymorphism / Genetic aspects / Genotyping / Glioblastoma / Glioblastoma multiforme / Health Promotion and Disease Prevention / Heterozygotes / Homozygotes / Informed consent / Kinases / Medical prognosis / Medicine/Public Health / Monoclonal antibodies / Oncology / Oncology, Experimental / Parenchyma / Pathogenesis / Patients / PCR–RFLP / Polymerase chain reaction / Polymorphism / Proteins / Radiation therapy / Restriction fragment length polymorphism / Serine / Surgery / Surgical Oncology / Targeted cancer therapy