Molecular subtypes based on immunologic and epithelial-mesenchymal transition gene sets reveal tumor immune microenvironment characteristics and implications for immunotherapy of patients with glioma

Abstract

The tumor immune microenvironment (TIME) significantly influences cancer progression and treatment. This study sought to uncover novel TIME-related glioma biomarkers to advance antitumor immunotherapies by integrating data from sequencing of bulk RNA as well as scRNA. Immunologic and epithelial-mesenchymal transition (EMT) characteristics were used to classify glioma patients into two immune subtypes (ISs) and two EMT subtypes (ESs). Patients in IS1 and ES1, characterized by high immune infiltration and low stemness scores, exhibited poor clinical outcomes and limited responsiveness to immunotherapy. A new risk signature was developed using 16 genes and validated in independent glioma cohorts. Among these, HAVCR2, IL18, LAGLS9, and PTPN6 emerged as hub genes, with IL18 identified as a potential independent indicator. The upregulation of IL18 in high-grade gliomas and U-251 MG cells aligned with bioinformatics analysis. These insights deepen the understanding of TIME-related mechanisms in glioma and highlight potential therapeutic targets, offering a theoretical foundation for effective antitumor immunotherapies in glioma.

Keywords

• Molecular subtypes
• Immunologic and epithelial-mesenchymal transition gene sets
• Tumor immune microenvironment
• Immunotherapy