VEGF Signaling Pathway Germline Polymorphisms as Prognostic Pharmacogenetic Biomarkers in Localized High-Grade Osteosarcoma Patients from the GEIS-33 Protocol
Year: 2025
Type: article
Abstract: Background/Objective: The vascular endothelial growth factor (VEGF) signaling pathway induces angiogenesis, which impacts tumor progression and clinical outcomes in patients with localized osteosarcoma. This study evaluates whether genetic polymorphisms in the VEGF signaling pathway are associated with survival outcomes in these patients. Methods: Sixty-nine patients with localized high-grade osteosarcoma enrolled in the GEIS-33 protocol and treated with MAP (methotrexate, doxorubicin, cisplatin) chemotherapy, surgery, and subsequent adjuvant treatment were included. Nine variants of interest in the VEGFA (rs1570360, rs2010963 and rs699947), FLT1 (VEGFR1; rs7993418, rs9513070 and rs9582036), and KDR (VEGFR2; rs1551641 and rs1870377 and rs2071559) genes were genotyped from peripheral blood samples using TaqMan Assay technology. Genetic data were correlated with relapse-free survival (RFS) and overall survival (OS) considering clinical variables as covariates. Results: The analyses showed nominally significant associations between the FLT1 variants rs7993418 and rs9582036 and survival. Patients carrying the rs7993418(C) allele had worse RFS (p = 0.01) and OS (p = 0.01). Carriers of the minor rs9582036(C) allele also had worse RFS (p = 0.02) and OS (p = 0.03). Additionally, patients harboring the TT genotype of the KDR rs1551641 variant had significantly worse RFS (p = 0.002). These polymorphisms remained statistically significant in the multivariate Cox regression analyses that included surgical margins and pathological response as covariates. Conclusions: Pharmacogenetics may contribute to precision medicine in oncology. Germline polymorphisms in the VEGF pathway may be useful as predictors of survival in high-grade localized osteosarcoma patients treated with chemotherapy, following validation in a large cohort of patients. Current treatment strategies aimed at improving outcomes for osteosarcoma patients may benefit from the identification of new biomarkers, such as these FLT1 rs7993418 and rs9582036 variants.
Source: Pharmaceuticals
DOI: 10.3390/ph18121855
Authors: Juliana Salazar, María J. Arranz, Javier Martin-Broto, Massimo Serra, Emanuela Palmerini, Jeronimo Martínez-García, Antonio Juan-Ribelles, Maitane Andion, Javier Martinez-Trufero, Guiomar Gutiérrez, Aizpea Echebarria-Barona, Maria A. Vaz-Salgado, Alexandra Regueiro, Rosa Alvarez, Claudia Valverde, Pablo Luna, Pilar Blay, Ana Sebio
Institutions: Institut de Recerca Sant Pau, University Hospital Mútua de Terrassa, Mútua Terrassa, Hospital Universitario Fundación Jiménez Díaz, Istituto Ortopedico Rizzoli, University of Miami, Sylvester Comprehensive Cancer Center, Hospital Universitario Virgen de la Arrixaca, Hospital Universitari i Politècnic La Fe, Hospital Infantil Universitario Niño Jesús, Hospital Universitario Miguel Servet, Hospital Regional Universitario de Málaga, Hospital de Cruces, Hospital Universitario Ramón y Cajal, Complejo Hospitalario Universitario de Santiago, Hospital General Universitario Gregorio Marañón, Vall d'Hebron Hospital Universitari, Vall d'Hebron Institute of Oncology, Hospital Universitario Son Espases, Hospital Universitario Central de Asturias, Hospital de Sant Pau
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $3,499
OpenAlex ID: W4417034937