Construction of Interferon-Gamma-Related Gene Signature to Characterize the Immune-Inflamed Phenotype of Glioblastoma and Predict Prognosis, Efficacy of Immunotherapy and Radiotherapy
Open Access
- 10 September 2021
- journal article
- research article
- Published by Frontiers Media SA in Frontiers in Immunology
Abstract
Interferon-gamma (IFNG) has profound impacts on tumor-immune interaction and is of great clinical significance for multiple cancers. Exploring the role of IFNG in glioblastoma (GBM) may optimize the current treatment paradigm of this disease. Here, multi-dimensional data of 429 GBM samples were collected. Various bioinformatics algorithms were employed to establish a gene signature that characterizes immunological features, genomic alterations, and clinical characteristics associated with the IFNG response. In this way, a novel IFNG-related gene signature (IFNGrGS, including TGFBI, IL4I1, ACP5, and LUM) has been constructed and validated. Samples with increased IFNGrGS scores were characterized by increased neutrophil and macrophage infiltration and exuberant innate immune responses, while the activated adaptive immune response may be frustrated by multiple immunosuppressive mechanisms. Notably, the IFNG pathway as well as its antagonistic pathways including IL4, IL10, TGF-beta, and VEGF converged on the expression of immune checkpoints. Besides, gene mutations involved in the microenvironment were associated with the IFNGrGS-based stratification, where the heterogeneous prognostic significance of EGFR mutation may be related to the different degrees of IFNG response. Moreover, the IFNGrGS score had solid prognostic value and the potential to screen ICB and radiotherapy sensitive populations. Collectively, our study provided insights into the role of IFNG on the GBM immune microenvironment and offered feasible information for optimizing the treatment of GBM.This publication has 91 references indexed in Scilit:
- GSVA: gene set variation analysis for microarray and RNA-Seq dataBMC Bioinformatics, 2013
- Ways to Enhance Lymphocyte Trafficking into Tumors and Fitness of Tumor Infiltrating LymphocytesFrontiers in Oncology, 2013
- Molecular signatures database (MSigDB) 3.0Bioinformatics, 2011
- GISTIC2.0 facilitates sensitive and confident localization of the targets of focal somatic copy-number alteration in human cancersGenome Biology, 2011
- CD8+ T-cell infiltrate in newly diagnosed glioblastoma is associated with long-term survivalJournal of Clinical Neuroscience, 2010
- edgeR: a Bioconductor package for differential expression analysis of digital gene expression dataBioinformatics, 2009
- Systematic and integrative analysis of large gene lists using DAVID bioinformatics resourcesNature Protocols, 2008
- Bioinformatics enrichment tools: paths toward the comprehensive functional analysis of large gene listsNucleic Acids Research, 2008
- Comprehensive genomic characterization defines human glioblastoma genes and core pathwaysNature, 2008
- Subclass Mapping: Identifying Common Subtypes in Independent Disease Data SetsPLOS ONE, 2007