Effects of VEGFA genetic polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors
10.19405/j.cnki.issn1000–1492.2026.05 014
- VernacularTitle:脑肿瘤患儿VEGFA基因多态性对化疗毒性和临床预后的影响研究
- Author:
Zhengyue LIU
1
;
Lingjia MENG
1
;
An YAN
1
;
Miao LI
1
;
Shumei WANG
1
Author Information
1. Department of Pharmacy, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038
- Publication Type:Journal Article
- Keywords:
brain tumor;
vascular endothelial growth factor A;
single nucleotide polymorphism;
chemotherapy toxicity;
prognosis
- From:
Acta Universitatis Medicinalis Anhui
2026;61(5):901-907
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the effects of vascular endothelial growth factor A (VEGFA) rs2010963 and rs3025039 polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors. MethodsA total of 104 pediatric patients with brain tumors receiving standardized chemotherapy were enrolled. Matrix-assisted laser desorption/ionization time of flight mass spectrometry was used for VEGFA rs2010963 and rs3025039 genotyping. The χ² test was applied to analyze the association between genotypes and chemotherapy‑related toxicities. Cox regression was used to evaluate the correlations of clinicopathological characteristics and genotypes with the progression‑free survival (PFS). In addition, bioinformatic analyses were conducted to investigate the regulatory factors potentially affected by the two SNP loci. ResultsThe VEGFA expression in brain tumors (5.17±1.81) was significantly higher than that in normal tissues (4.33±1.56, P<0.001). Patients with high VEGFA expression had significantly worse overall survival than patients with low VEGFA expression (P<0.001). Among the 104 children with brain tumors included, the rs2010963 CC, CG, and GG genotypes accounted for 14.42%, 55.77%, and 29.81%, respectively. The frequencies of C and G alleles were 42.31% and 57.69%, respectively. The rs3025039 CC, CT, and TT genotypes accounted for 70.19%, 25.96%, and 3.85%, respectively. The frequencies of C and T alleles were 83.17% and 16.83%, respectively. The children with the rs3025039 CC genotype had significantly higher incidences of thrombocytopenia (46.58%) and gastrointestinal toxicity (56.16%) than CT genotype carriers (22.22% and 33.33%, respectively, P<0.05), and significantly lower incidences of coagulation disorders (4.11%) than TT genotype carriers (50.00%, P<0.05).The incidence of hyperlipidemia (2.74%) was significantly lower than that in the CT genotype carriers (14.82%, P<0.05). The tumor type and the rs2010963 genotype were significantly associated with PFS (P<0.05) in univariable and multivariable Cox regression analysis. Bioinformatic analysis indicated that the rs2010963 and rs3025039 polymorphisms regulated VEGFA expression by affecting the binding of transcription factors and miRNAs to their target gene sequences, respectively. ConclusionThe VEGFA rs3025039 CC genotype is a risk factor for thrombocytopenia and gastrointestinal toxicity, and a protective factor for coagulation disorders and hyperlipidemia. The rs2010963 CG genotype is a protective factor for brain tumor progression.