Abstract
Osteosarcoma (OS) is a prevalent form of bone cancer among younger people, particularly children and adolescents. Ferroptosis is a non-apoptotic cell death identified by increased levels of iron-dependent lipid peroxidation. This study was designed to develop a prognostic model based on differentially expressed genes (DEGs) associated with ferroptosis and examined the functions of ferroptosis-related genes (FRGs) in OS cells. Gene expression profiles in OS were retrieved from TARGET and GEO databases, while GTEx provided data for healthy tissues. Prognostic genes were identified through bioinformatics analysis and data integration. In vitro experiments, cell cultures, qRT-PCR, immunohistochemistry (IHC), cell transfection, Edu assays, DHE assays, migration, and invasion assays validated the prognostic model and explored the functional role of FRGs in OS cells. Univariate Cox regression analysis demonstrated that 12 DEGs were differentially expressed. Based on four FRGs in OS constructed a risk-scoring model. The high-risk (HR) group showed a considerably lower OS rate than the low-risk (LR) group (p < 0.001 in the TARGET and p < 0.05 in the GSE21257 cohorts). A risk score was validated as an independent predictive factor for OS via multivariate Cox regression. Functional analysis shows that these FRGs affect the occurrence of ferroptosis by influencing the intracellular ROS levels and play a regulatory role in the proliferation, migration, and infiltration of OS cells. The findings suggested that four FRGs demonstrate significant prognostic value in OS, offering potential insights into novel therapeutic targets for OS treatment.