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VEGF Signaling Pathway Germline Polymorphisms as Prognostic Pharmacogenetic Biomarkers in Localized High-Grade
Juliana Salazar1, María J Arranz2, Javier Martin-Broto3
1Translational Medical Oncology Laboratory, Institut de Recerca Sant Pau (IR Sant Pau), 08041 Barcelona, Spain.
Pharmaceuticals (Basel, Switzerland)
|December 31, 2025
Summary
Genetic variations in the vascular endothelial growth factor (VEGF) pathway impact survival for localized osteosarcoma patients. Specific FLT1 and KDR gene variants are associated with poorer relapse-free and overall survival in these patients.
Area of Science:
- Oncology
- Genetics
- Pharmacogenetics
Background:
- The vascular endothelial growth factor (VEGF) signaling pathway is crucial for angiogenesis, influencing tumor progression and outcomes in localized osteosarcoma.
- Understanding genetic predispositions within the VEGF pathway may offer insights into patient prognosis and personalized treatment strategies.
Purpose of the Study:
- To investigate the association between genetic polymorphisms in the VEGF signaling pathway and survival outcomes in patients with localized high-grade osteosarcoma.
- To identify potential genetic biomarkers for predicting prognosis in osteosarcoma patients undergoing chemotherapy.
Main Methods:
- Genotyping of nine variants in VEGFA, FLT1 (VEGFR1), and KDR (VEGFR2) genes from peripheral blood samples of 69 localized high-grade osteosarcoma patients.
- Analysis of relapse-free survival (RFS) and overall survival (OS) in correlation with genetic polymorphisms, adjusting for clinical covariates like surgical margins and pathological response.
- Utilized TaqMan Assay technology for genotyping and multivariate Cox regression for statistical analysis.
Main Results:
- Significant associations were found between FLT1 variants (rs7993418 and rs9582036) and survival outcomes; carriers of specific alleles (rs7993418(C) and rs9582036(C)) exhibited worse RFS and OS.
- The KDR rs1551641 (TT genotype) was significantly associated with worse RFS.
- These associations remained statistically significant after multivariate analysis, indicating their independent predictive value.
Conclusions:
- Germline polymorphisms in the VEGF pathway, particularly in FLT1, may serve as predictive biomarkers for survival in localized high-grade osteosarcoma patients.
- Pharmacogenetics holds potential for advancing precision medicine in osteosarcoma treatment.
- Further validation in larger cohorts is recommended to confirm the clinical utility of these genetic markers.
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