Background: Glioblastoma (GBM) is the most common type of brain cancer with poor survival outcomes and unsatisfactory response to current therapeutic strategies. Recent studies have demonstrated that ferroptosis-related genes (FRGs) are linked with the occurrence and development of GBM and may become promising biological indicators in GBM therapy.

Methods: We systematically assessed the relationship between FRGs expression profiles and prognosis in glioma patients based on the Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) datasets to establish a risk score model according to the gene signature of multiple survival-associated DEGs. Further, the differences between the tumor microenvironment score, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity in the high- and low-risk group are analyzed through a variety of algorithms in R software.

Results: GBM patients were divided into two subgroups (high- and low-risk) according to the established risk score model. Patients in the high-risk group showed significantly reduced overall survival compared with those in the low-risk group. Also, we found that the high-risk group showed higher ImmuneScore and StromalScore, while different subgroups have significant differences in immune cell infiltration, immune checkpoint expression levels, and drug sensitivity. In summary, we developed and validated an FRGs risk model, which served as an independent prognostic indicator for GBM. Besides, the two subgroups divided by the model have significant differences, which provides novel insights for further studies as well as the personalized treatment of patients.