Prognostic Prediction Model for Glioblastoma: A Ferroptosis-Related Gene Prediction Model and Independent External Validation

Wenlin Chen; Chuxiang Lei; Yuekun Wang; Dan Guo; Sumei Zhang; Xiaoxi Wang; Zixin Zhang; Yu Wang; Wenbin Ma

doi:10.3390/jcm12041341

Prognostic Prediction Model for Glioblastoma: A Ferroptosis-Related Gene Prediction Model and Independent External Validation

J Clin Med. 2023 Feb 8;12(4):1341. doi: 10.3390/jcm12041341.

Authors

Wenlin Chen¹, Chuxiang Lei², Yuekun Wang¹, Dan Guo³, Sumei Zhang³, Xiaoxi Wang³, Zixin Zhang³, Yu Wang¹, Wenbin Ma¹

Affiliations

¹ Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.
² Department of Cardiac Surgery, State Key Laboratory of Cardiovascular Diseases, National Center for Cardiovascular Diseases, Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100037, China.
³ Clinical Biobank, Medical Research Center, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China.

Abstract

Glioblastoma (GBM) is the most common primary malignant intracranial tumor with a poor prognosis. Ferroptosis is a newly discovered, iron-dependent, regulated cell death, and recent studies suggest its close correlation to GBM. The transcriptome and clinical data were obtained for patients diagnosed with GBM from TCGA, GEO, and CGGA. Ferroptosis-related genes were identified, and a risk score model was constructed using Lasso regression analyses. Survival was evaluated by univariate or multivariate Cox regressions and Kaplan-Meier analyses, and further analyses were performed between the high- and low-risk groups. There were 45 ferroptosis-related different expressed genes between GBM and normal brain tissues. The prognostic risk score model was based on four favorable genes, CRYAB, ZEB1, ATP5MC3, and NCOA4, and four unfavorable genes, ALOX5, CHAC1, STEAP3, and MT1G. A significant difference in OS between high- and low-risk groups was observed in both the training cohort (p < 0.001) and the validation cohorts (p = 0.029 and 0.037). Enrichment analysis of pathways and immune cells and functioning was conducted between the two risk groups. A novel prognostic model for GBM patients was developed based on eight ferroptosis-related genes, suggesting a potential prediction effect of the risk score model in GBM.

Keywords: differently expressed genes; ferroptosis; glioblastoma; prognosis; risk score.

Grants and funding

This work was funded by the Beijing Municipal Natural Science Foundation (7202150) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-019) for Yu Wang, and by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-113), the Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (2019ZLH101) and the Beijing Municipal Natural Science Foundation (19JCZDJC64200[Z]) for Wenbin Ma.