Ferroptosis-related gene signature correlates with the tumor immune features and predicts the prognosis of glioma patients.

Yan Hu,Kai Huang,Zewei Tu,Xingen Zhu,Kunjian Lei

doi:10.1042/bsr20211640

Abstract

Background: Glioma is a malignant intracranial tumor and the most fatal cancer. The role of ferroptosis in the clinical progression of gliomas is unclear.Method: Univariate and least absolute shrinkage and selection operator (Lasso) Cox regression methods were used to develop a ferroptosis-related signature (FRSig) using a cohort of glioma patients from the Chinese Glioma Genome Atlas (CGGA), and was validated using an independent cohort of glioma patients from The Cancer Genome Atlas (TCGA). A single-sample gene set enrichment analysis (ssGSEA) was used to calculate levels of the immune infiltration. Multivariate Cox regression was used to determine the independent prognostic role of clinicopathological factors and to establish a nomogram model for clinical application.Results: We analyzed the correlations between the clinicopathological features and ferroptosis-related gene (FRG) expression and established an FRSig to calculate the risk score for individual glioma patients. Patients were stratified into two subgroups with distinct clinical outcomes. Immune cell infiltration in the glioma microenvironment and immune-related indexes were identified that significantly correlated with the FRSig, the tumor mutation burden (TMB), copy number alteration (CNA), and immune checkpoint expression was also significantly positively correlated with the FRSig score. Ultimately, an FRSig-based nomogram model was constructed using the independent prognostic factors age, World Health Organization (WHO) grade, and FRSig score.Conclusion: We established the FRSig to assess the prognosis of glioma patients. The FRSig also represented the glioma microenvironment status. Our FRSig will contribute to improve patient management and individualized therapy by offering a molecular biomarker signature for precise treatment.

Highlights

濄濌澳 ABSTRACT 濅濃澳 Background: Glioma is a malignant intracranial tumor and the most fatal cancer
Multivariate Cox 濅濊澳 regression was used to determine the independent prognostic role of clinicopathological factors 濅濋澳 and to establish a nomogram model for clinical application.Results: We analyzed the 濅濌澳 correlations between the clinicopathological features and ferroptosis-related gene (FRG) 濆濃澳 expression and established a ferroptosis-related signature (FRSig) to calculate the risk score for individual glioma patients. 濆濄澳 Patients were stratified into two subgroups with distinct clinical outcomes
The results showed that expression of 濄濋濉澳 zinc finger E-box binding homeobox 1 (ZEB1), nuclear receptor coactivator 4 (NCOA4), SLC11A2, transferrin 濄濃濃澳 receptor (TFRC), SLC1A5, HSPB1, ferritin heavy chain 1 (FTH1), and ferritin light chain (FTL) differed significantly 濄濋濊澳 between LGGs with mutated IDH and wildtype-IDH LGGs in the Chinese Glioma Genome Atlas (CGGA) datasets (Figure 2C). 濄濋濋澳 SLC1A5, FTH1, FTL, HSPB1, NCOA4, SLC11A2, ZEB1, and TFRC genes were 濄濋濌澳 differentially expressed in GBM patients with and without IDH mutation in the CGGA dataset 濄濌濃澳 (Figure 2D)

Summary

Introduction

濄濌澳 ABSTRACT 濅濃澳 Background: Glioma is a malignant intracranial tumor and the most fatal cancer. Multivariate Cox 濅濊澳 regression was used to determine the independent prognostic role of clinicopathological factors 濅濋澳 and to establish a nomogram model for clinical application.Results: We analyzed the 濅濌澳 correlations between the clinicopathological features and ferroptosis-related gene (FRG) 濆濃澳 expression and established a FRSig to calculate the risk score for individual glioma patients.

Results

Conclusion