A Risk-Scoring Model Based on Evaluation of Ferroptosis-Related Genes in Osteosarcoma.

Abstract

Background Osteosarcoma (OS) is a bone malignancy frequently seen in pediatrics and has high mortality and incidence. Ferroptosis is an important cell death process in regulating the apoptosis and invasion of tumor cells, so constructing the risk-scoring model based on OS ferroptosis-related genes (FRGs) will benefit the evaluation of both treatment and prognosis. Methods The OS dataset was screened from the Therapeutically Applicable Research to Generate Effective Treatments (TARGET) database, and OS-related FRGs were found through the Ferroptosis Database (FerrDb) using a multivariate Cox regression model, followed by the generation of the risk scores and a risk-scoring prediction model. Further systematical exploration for immune cell infiltration and assessing the prediction of response to targeted drugs was conducted. Results Based on OS-related FRGs, a risk-scoring model of FRGs in OS was constructed. The six FRGs played a role in the carbon metabolism, glutathione metabolism, and pentose phosphate pathways. Results from targeted drug sensitivity analyses were concordant to pathway analyses. The response to targeted drugs statistically differed between the two groups with different risks, and the high-risk group presented a high sensitivity to targeted drugs. Conclusions We identified a 6-ferroptosis-gene-based prognostic signature in OS and created and verified a risk-scoring model to predict the prognosis of OS at 1, 3, and 5 years for OS patients independently.