Construction of a prognostic classifier and prediction of the immune landscape and immunosuppressive molecules in gliomas based on combination of inflammatory response-related genes and angiogenesis-associated genes

Abstract

Objective:We aimed to combine inflammatory response-related genes (IRRGs) and angiogenesis-associated genes (AAGs) to build a prognostic classifier and to predict immune landscapes and immunosuppressive molecules in gliomas. Introduction: Gliomas, the commonest primary brain tumors, account for about 80% of cancerous tumors in the central nervous system (CNS), featuring rapid progression, high malignancy, and extremely poor prognosis. The induction of inflammatory responses and angiogenesis have been considered to be closely related to tumors. However, there are little publications systematically elaborating on their impacts on gliomas. Methods: We downloaded the data of IRRGs and AAGs from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA) databases, and retrieved 68 differentially expressed genes (DEGs), of which 13 DEGs pertained to the prognosis of glioma cases. Next, 9 DEGs were screened from the 13 major DEGs with predictive significance and utilized to build a 9-gene signature as a prognostic risk score model (PRSM) with the aid of univariate Cox regression analyses (CRA) and least absolute shrinkage and selection operator (LASSO)-CRA. On this basis, glioma patients fell into high-risk (HR) group and low-risk (LR) group. Later, we implemented Gene Set Enrichment Analysis (GSEA, Gene Set: WP_ANGIOGENESIS) and calculate the scores of cell infiltration and immune-associated function by harnessing single-sample GSEA (ssGSEA). Results: The prognosis was compared between the two groups by introducing Kaplan-Meier (KM) analysis, which yielded that HR group exhibited poorer prognosis. Additionally, the predictive capacity and independent characteristics were proven by the receiver operating characteristic curve (ROC) and multivariate CRA. Further, We took an evaluation of immune profiles, which unraveled that immunosuppressive cell count was distinctively larger in HS group. Finally, a protein-protein interaction (PPI) network of DEGs was built, and 10 hub genes were obtained, of which epidermal growth factor receptor (EGFR) was closely related to poor prognosis. Conclusion: A 9-gene signature was established on the strength of IRRGs and AAGs for predicting glioma prognosis, tumor microenvironment (TME), immune landscapes and immunosuppressive molecules. However, the molecular mechanism developed by this signature to function in tumor immunity needs further experimental research in the future and is expected to be a research target for glioma immunotherapy strategies.