Novel Immune-Related Gene-Based Signature Characterizing an Inflamed Microenvironment Predicts Prognosis and Radiotherapy Efficacy in Glioblastoma

Hang Ji; Hongtao Zhao; Jiaqi Jin; Zhihui Liu; Xin Gao; Fang Wang; Jiawei Dong; Xiuwei Yan; Jiheng Zhang; Nan Wang; Jianyang Du; Shaoshan Hu

doi:10.3389/fgene.2021.736187

Novel Immune-Related Gene-Based Signature Characterizing an Inflamed Microenvironment Predicts Prognosis and Radiotherapy Efficacy in Glioblastoma

Front Genet. 2022 Jan 17:12:736187. doi: 10.3389/fgene.2021.736187. eCollection 2021.

Authors

Hang Ji^{1

2

3}, Hongtao Zhao^{1

2}, Jiaqi Jin^{2

4}, Zhihui Liu², Xin Gao^{1

2}, Fang Wang^{1

2}, Jiawei Dong^{1

2}, Xiuwei Yan^{1

2}, Jiheng Zhang^{1

2}, Nan Wang^{1

2}, Jianyang Du⁵, Shaoshan Hu^{1

2}

Affiliations

¹ Department of Neurosurgery, Zhejiang Provincial People's Hospital, Hangzhou, China.
² Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, China.
³ Translational Medicine Research and Cooperation Center of Northern China, Heilongjiang Academy of Medical Sciences, Harbin, China.
⁴ The Key Laboratory of Myocardial Ischemia, Ministry of Education, Harbin, China.
⁵ Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, China.

Abstract

Effective treatment of glioblastoma (GBM) remains an open challenge. Given the critical role of the immune microenvironment in the progression of cancers, we aimed to develop an immune-related gene (IRG) signature for predicting prognosis and improving the current treatment paradigm of GBM. Multi-omics data were collected, and various bioinformatics methods, as well as machine learning algorithms, were employed to construct and validate the IRG-based signature and to explore the characteristics of the immune microenvironment of GBM. A five-gene signature (ARPC1B, FCGR2B, NCF2, PLAUR, and S100A11) was identified based on the expression of IRGs, and an effective prognostic risk model was developed. The IRG-based risk model had superior time-dependent prognostic performance compared to well-studied molecular pathology markers. Besides, we found prominent inflamed features in the microenvironment of the high-risk group, including neutrophil infiltration, immune checkpoint expression, and activation of the adaptive immune response, which may be associated with increased hypoxia, epidermal growth factor receptor (EGFR) wild type, and necrosis. Notably, the IRG-based risk model had the potential to predict the effectiveness of radiotherapy. Together, our study offers insights into the immune microenvironment of GBM and provides useful information for clinical management of this desperate disease.

Keywords: EGFR; glioblastoma; immune checkpoint blockade therapy; immune microenvironment; immune-related gene; prognosis; radiotherapy.