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.

Ferroptosis in osteosarcoma: A promising future

“…A number of studies have analyzed differentially expressed genes and long non-coding RNAs (lncRNAs) during ferroptosis in OS through bioinformatics, and finally identified 26 genes associated with OS prognosis ( 69 – 73 ) (CBS, EGFR, COCS1, PTN, PGD, ZEP36, DLL1, EOMES, ERCC2, G6PD, MYC, SLC39A8, etc.) and 8 lncRNAs ( 74 , 75 ) (RPARP-AS1, PARD6G-AS1, GAS5, UNC5B -AS1, LINC01060, AC124798.1, AC090559.1, and AC104825.1), which created a new prognostic model for OS patients.…”

A ferroptosis-related gene signature associated with immune landscape and therapeutic response in osteosarcoma

“…Thirdly, ferroptosis-related gene signature for OS is not a novel subject. Lei et al (95), Zhao et al (96), Jiang et al (97) all reported prognostic ferroptosis signatures, which might make our finding less novel. However, our study appears to be the first to reveal the correlation between immune landscape and ferroptosis signature from the perspective of a single-cell sequence.…”

MAT2A inhibits the ferroptosis in osteosarcoma progression regulated by miR-26b-5p

“…Cells undergo ferroptosis as part of their apoptosis, invasion, and metastasis processes. Divalent iron or ester oxygenase is present during ferroptosis, which catalyzes the reduction of lipid-derived unsaturated fatty acids from cell membranes, causing lipid peroxidation and induces cell death [5] , [6] . Ferroptosis terminates in mitochondrial dysfunction and toxic lipid peroxidation [6] .…”