Identification of an IL-4-Related Gene Risk Signature for Malignancy, Prognosis and Immune Phenotype Prediction in Glioma

Abstract

Background: Emerging molecular and genetic biomarkers have been introduced to classify gliomas in the past decades. Here, we introduced a risk signature based on the cellular response to the IL-4 gene set through Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. Methods: In this study, we provide a bioinformatic profiling of our risk signature for the malignancy, prognosis and immune phenotype of glioma. A cohort of 325 patients with whole genome RNA-seq expression data from the Chinese Glioma Genome Atlas (CGGA) dataset was used as the training set, while another cohort of 667 patients from The Cancer Genome Atlas (TCGA) dataset was used as the validating set. The LASSO model identified a 10-gene signature which was considered as the optimal model. Results: The signature was confirmed to be a good predictor of clinical and molecular features involved in the malignancy of gliomas. We also identified that our risk signature could serve as an independently prognostic biomarker in patients with gliomas (p < 0.0001). Correlation analysis showed that our risk signature was strongly correlated with the Tregs, M0 macrophages and NK cells infiltrated in the microenvironment of glioma, which might be a supplement to the existing incomplete innate immune mechanism of glioma phenotypes. Conclusions: Our IL-4-related gene signature was associated with more aggressive and immunosuppressive phenotypes of gliomas. The risk score could predict prognosis independently in glioma, which might provide a new insight for understanding the IL-4 involved mechanism of gliomas.

Construction and validation of an angiogenesis-related gene expression signature associated with clinical outcome and tumor immune microenvironment in glioma

“…Furthermore, we compared the prognostic predictive abilities of 20 different risk signatures of gliomas in TCGA from published articles, including inflammatory response-related gene (IRRG) signature ( Yan et al, 2022 ), DNA damage and repair-related gene (DDRRG) signature ( Li et al, 2022c ), CXCR members signature ( He et al, 2022 ), pyroptosis-related gene signature ( Zhang M. et al, 2021b ; Chao et al, 2022 ; Yang et al, 2022 ; Zhang et al, 2022 ), ECM-related gene (ECMRG) signature ( Li et al, 2022b ), tripartite motif (TRIM) family gene signature ( Xiao et al, 2022 ), antigen presentation machinery (APM) signature ( Chen et al, 2022 ), natural killer cell-related gene (NKRG) signature ( Li C. et al, 2022a ), IL-4-related gene (IL4RG) signature ( Qi et al, 2022 ), hypoxia-related gene (HRG) signature ( Gao et al, 2021 ), S100 family-based signature ( Hu et al, 2021 ), TIME signature ( Zhang C. et al, 2021a ), focal adhesion-related gene (FARG) signature ( Li et al, 2021 ), m6A RNA methylation regulator signature ( Cong et al, 2021 ), HDAC1-related signature ( Fan et al, 2021 ), RNA-binding protein (RBP)-based signature ( Chen et al, 2021a ) and ferroptosis-related gene (FRG) signature ( Chen et al, 2021b ). The results of univariate and multivariate Cox analyses showed that our ARG signature had independent predictive ability ( p < 0.001, Table 1 ).…”

A Metabolic Plasticity-Based Signature for Molecular Classification and Prognosis of Lower-Grade Glioma

“…Polymorphisms in the interleukin-4 receptor genes are associated with better OS in Glioma patients [ 31 ]. The interleukin-4-related genes have a prognostic value for Glioma [ 32 ].…”

A lipid metabolism-related risk signature for patients with gliomas constructed with TCGA and CGGA data

“…Although the high-risk group showed enrichment of more types of immune cells than the low-risk group, Treg cells and M0 macrophages have been reported to play an immunosuppressive role in gliomas, and Treg cells, neutrophils and M0 macrophages are associated with the malignant clinical features of gliomas, indicating the predominance of cancer-promoting immune cells in the high-risk group. [39][40][41][42] The monocytes that were enriched in the low-risk group were antigen-presenting cells that elicited significant antitumor effects. [43] Interestingly, the levels of infiltrating CD8 + and CD4 + T cells in high-risk patients with gliomas were higher than those in low-risk patients.…”