A Ferroptosis-Related Prognostic Risk Score Model to Predict Clinical Significance and Immunogenic Characteristics in Glioblastoma Multiforme.

Dongdong Xiao,Chuansheng Nie,Xuan Wang,Xiaobing Jiang,Hongyang Zhao,Yujie Zhou,Xiangpan Li

doi:10.1155/2021/9107857

Abstract

Background Ferroptosis is a recently identified cell death pathway, and the susceptibility to ferroptosis inducers varies among cancer cell types. There have been recent attempts to clarify the mechanisms implicated in ferroptosis, glioma invasion, and the immune microenvironment but little is known about ferroptosis regulation in GBM. Methods Screening ferroptosis-related genes from published reports and existing databases, we constructed an integrated model based on the RNA-sequencing data in GBM. The association of FRGPRS and overall survival is identified and validated across several different datasets. Genomic and clinical characteristics, immune infiltration, enriched pathways, pan-cancer, drug resistance, and immune checkpoint inhibitor therapy are compared among various FRGPRS subgroups. Results We identified and confirmed the influences of five ferroptosis key hub genes in the FRGPRS model. The FRGPRS model could serve to predict overall survival and progression-free survival in GBM patients, and high FRGPRS was associated with comparatively stronger immunity, higher proportions of tumour tissue, and good cytolytic immune and chemotherapeutics response in GBM patients. Conclusions The five ferroptosis key hub genes constituting the FRGPRS model could serve to predict overall survival and progression-free survival in patients with GBM and help guide timely and efficacious therapeutic strategies customised and optimised for each individual patient. This discovery may lay the foundation for the development and optimisation of other iterations of this model for the improved forecasting, detection, and treatment of other malignancies notorious for their drug resistance and immune escape.

Highlights

Glioblastoma multiforme (GBM) is a primary malignant brain tumour
We assessed the expression profiles of preprocessed GBM and normal brain tissue sample data downloaded from The Cancer Genome Atlas (TCGA) and GTEx
Ferroptosis-Related Gene Prognostic Risk Score (FRGPRS) was significantly correlated with CAN and reflected the predictive power of gene mutation and immune infiltration, and these were closely related to clinical features, outcome, recurrence, and immune function

Summary

Introduction

Glioblastoma multiforme (GBM) is a primary malignant brain tumour. Despite the fact that it is treated with multidisciplinary synthetic therapy, including surgical resection, radiotherapy, and chemotherapy, the patients’ overall survival time is only approximately 15 months [1, 2]. Extensive tumour tissue hypoxia together with rapid tumour expansion triggers necrosis They comprise the fundamental stimuli of GBM stem cell progression [7]. The five ferroptosis key hub genes constituting the FRGPRS model could serve to predict overall survival and progression-free survival in patients with GBM and help guide timely and efficacious therapeutic strategies customised and optimised for each individual patient. This discovery may lay the foundation for the development and optimisation of other iterations of this model for the improved forecasting, detection, and treatment of other malignancies notorious for their drug resistance and immune escape

Methods

Results

Conclusion