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


Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
20 Sep 2023
Historique:
received: 30 05 2023
accepted: 13 09 2023
medline: 22 9 2023
pubmed: 21 9 2023
entrez: 20 9 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 37730565
doi: 10.1186/s12885-023-11400-5
pii: 10.1186/s12885-023-11400-5
pmc: PMC10510274
doi:

Substances chimiques

Bevacizumab 2S9ZZM9Q9V
Arginine 94ZLA3W45F
Codon 0
CDKN1A protein, human 0
Cyclin-Dependent Kinase Inhibitor p21 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

886

Informations de copyright

© 2023. BioMed Central Ltd., part of Springer Nature.

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Auteurs

Wen-Yu Cheng (WY)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan. wycheng07@yahoo.com.tw.
Department of Physical Therapy, Hung Kuang University, Taichung city, Taiwan. wycheng07@yahoo.com.tw.
Institute of Biomedical Sciences, National Chung Hsing University, Taichung city, Taiwan. wycheng07@yahoo.com.tw.
Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung city, Taiwan. wycheng07@yahoo.com.tw.

Chiung-Chyi Shen (CC)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.
Department of Physical Therapy, Hung Kuang University, Taichung city, Taiwan.
Basic Medical Education, Central Taiwan University of Science and Technology, Taichung city, Taiwan.

Yea-Jiuen Liang (YJ)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.

Ming-Tsang Chiao (MT)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.

Yi-Chin Yang (YC)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.

Wan-Yu Hsieh (WY)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.

Cheng-Hui Lin (CH)

Department of Minimally Invasive Skull Base Neurosurgery, Neurological Institute, Taichung Veterans General Hospital, Taichung city, Taiwan.

Jun-Peng Chen (JP)

Biostatistics Task Force, Taichung Veterans General Hospital, Taichung city, Taiwan.

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