Effects of VEGFA genetic polymorphisms on chemotherapy toxicities and clinical prognosis in children with brain tumors

Acta Universitatis Medicinalis Anhui     font:big middle small

Fund programs: National Natural Science Foundation of China(No. 81872926)

Authors:Liu Zhengyue,Meng Lingjia,Yan An,Li Miao,Wang Shumei

Keywords:brain tumor;vascular endothelial growth factor A;single nucleotide polymorphism;chemotherapy toxicity;prognosis

DOI:10.19405/j.cnki.issn1000–1492.2026.05.014

〔Abstract〕 Objective To 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. Meth ⁃ ods A 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 charac ‑ teristics and genotypes with the progression‑free survival(PFS). In addition,bioinformatic analyses were con ‑ ducted to investigate the regulatory factors potentially affected by the two SNP loci. Results The VEGFA expres‑ sion 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 expres‑ sion(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 gastroin‑ testinal toxicity(56. 16%)than CT genotype carriers(22. 22% and 33. 33%,respectively,P<0. 05),and signifi‑ cantly lower incidences of coagulation disorders(4. 11%)than TT genotype carriers(50. 00%,P<0. 05). The inci‑ dence 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 univari‑ able 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. Conclusion The VEGFA rs3025039 CC genotype is a risk factor for thrombo ‑ cytopenia and gastrointestinal toxicity,and a protective factor for coagulation disorders and hyperlipidemia. The rs2010963 CG genotype is a protective factor for brain tumor progression.