A comprehensive analysis of ferroptosis-related metastasis genes in osteosarcoma.
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BACKGROUND: Osteosarcoma (OS) is an increasingly common primary bone tumor in children and adolescents, characterized by rapid local infiltration, distant metastasis, high invasiveness, and poor drug sensitivity. Ferroptosis is a programmed cell death caused by iron dependent, lipid peroxidation accumulation, ultimately leading to the destruction of cell membrane structure and function, resulting in cell death. However, the specific role of ferroptosis-related metastasis genes (FRMGs) in the pathogenesis of osteosarcoma is still unclear. METHODS: Utilize GEO database to obtain genetic and clinical information of osteosarcoma patients. Perform cluster analysis on FRMG using Consensus ClusterPlus. We conducted pathway enrichment analysis on DEGs from different subgroups using Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO). We used the Lasso regression model to construct line scores, and in order to improve the predictive ability of the model, we created a prediction bar chart and used a calibration curve. Finally, we used Oncoredist to compare drug sensitivity between high-risk and low-risk cohorts. RESULTS: In the clustering model, the survival time of patients in the C2 subgroup is higher than that of patients in the C1 subgroup. Pathway enrichment analysis showed that Glycan biosynthesis pathway, Spliceosome pathway, and Ubiquitin medtated proteoiysis pathway was enriched in osteosarcoma patients in group C1, while Glycosphingolipid biosynthsis pathway was enriched in osteosarcoma patients in group C2. In the Lasso regression model, the survival rate of high-risk scoring patients is significantly lower than that of low-risk scoring patients, and the risk score of C1 subgroup patients is significantly higher than that of C2 subgroup patients. The results of drug sensitivity analysis indicate that patients with low-risk scores are more sensitive to drugs. Patients with high expression of the FH gene in the risk model of osteosarcoma have a poorer prognosis, while those with high expression of the IL1B and SNCA genes in the risk model have a better prognosis. The single-cell analysis results showed that IL1B had the highest expression in monocytes/crops. The 3-year and 5-year survival values predicted by the ROC curve are 0.79 and 0.84, respectively, indicating the reliability of our prediction model. CONCLUSION: This study proposes a clinically applicable prognostic model based on ferroptosis-related metastasis genes, which provides insights into risk stratification and treatment decision-making for osteosarcoma, and provides a potential reference for risk stratification and therapeutic decision-making in osteosarcoma.