Background: Glioma is the most common cancer of the central nervous system with poor therapeutic response and clinical prognosis. Insulin-like growth factor 1 receptor (IGF-1R) signaling is implicated in tumor development and progression and induces apoptosis of cancer cells following functional inhibition. However, the relationship between the IGF-1R-related signaling pathway genes and glioma prognosis or immunotherapy/chemotherapy is poorly understood.Methods: LASSO–Cox regression was employed to develop a 16-gene risk signature in the TCGA-GBMLGG cohort, and all patients with glioma were divided into low-risk and high-risk subgroups. The relationships between the risk signature and the tumor immune microenvironment (TIME), immunotherapy response, and chemotherapy response were then analyzed. Immunohistochemistry was used to evaluate the HSP90B1 level in clinical glioma tissue.Results: The gene risk signature yielded superior predictive efficacy in prognosis (5-year area under the curve: 0.875) and can therefore serve as an independent prognostic indicator in patients with glioma. The high-risk subgroup exhibited abundant immune infltration and elevated immune checkpoint gene expression within the TIME. Subsequent analysis revealed that patients in the high-risk subgroup benefited more from chemotherapy. Immunohistochemical analysis confirmed that HSP90B1 was overexpressed in glioma, with significantly higher levels observed in glioblastoma than in astrocytoma or oligodendrocytoma.Conclusion: The newly identified 16-gene risk signature demonstrates a robust predictive capacity for glioma prognosis and plays a pivotal role in the TIME, thereby offering valuable insights for the exploration of novel biomarkers and targeted therapeutics.

Glioma has a poor prognosis, which is attributable to its inherent characteristics and lack of specific treatments. Immunotherapy plays a pivotal role in the contemporary management of malignancies. Despite the initiation of numerous immunotherapy-based clinical trials, their effects on enhancing glioma prognosis remain limited, highlighting the need for innovative and effective therapeutic targets and strategies to address this challenge. Since the 1990s, there has been a growing interest in cancer-testis antigens (CTAs) present in normal mammalian testicular germ cells and placental trophoblast cells, which exhibit reactivated expression in various tumor types. Mechanisms such as DNA methylation, histone modification, transcriptional regulation, and alternative splicing influence the expression of CTAs in tumors. The distinct expression patterns and robust immunogenicity of CTAs are promising tumor biomarkers and optimal targets for immunotherapy. Previous reports have shown that multiple CTAs are present in gliomas and are closely related to prognosis. The expression of these antigens is also associated with the immune response in gliomas and the effectiveness of immunotherapy. Significantly, numerous clinical trials, with IL13RA2 as a representative CTA member, have assessed the immunotherapeutic potential of gliomas and have shown favorable clinical efficacy. This review provides a comprehensive overview of the regulation and function of CTAs, summarizes their expression and role in gliomas, emphasizes their importance as immunotherapy targets in gliomas, and discusses related challenges and future interventions.

Clinical data indicates that glioma patients have poor treatment outcomes and clinical prognosis. The role of olfactory signaling pathway-related genes (OSPRGs) in glioma has not been fully elucidated. In this study, we aimed to investigate the role and relationship between OSPRGs and glioma. Univariate and multivariate Cox regression analyses were performed to assess the relationship between OSPRGs and the overall survival of glioma based on public cohorts, and the target gene (G Protein Subunit Alpha L, GNAL) was screened. The association of GNAL expression with clinicopathological characteristics, gene mutation landscape, tumor immune microenvironment (TIME), deoxyribonucleic acid (DNA) methylation, and naris-occlusion controlled genes (NOCGs) was performed. Immunohistochemistry was used to evaluate GNAL level in glioma. Further analysis was conducted to evaluate the drug sensitivity, immunotherapy response, and functional enrichment of GNAL. GNAL was an independent prognostic factor, and patients with low GNAL expression have a poor prognosis. Expression of GNAL was closely associated with clinicopathological characteristics, DNA methylation, and several immune-related pathways. Immune infiltration analysis indicated that GNAL levels were negatively correlated with immune scores. GNAL low-expression group showed efficacy with anti-PD-1 therapy. Ten compounds with significantly different half-maximal inhibitory concentration (IC50) values between the GNAL high and low-expression groups were identified. Furthermore, its expression was associated with several immune cells, immune-related genes, and NOCGs. The expression of GNAL is closely associated with clinicopathological characteristics, TIME, and the response to therapeutic interventions, highlighting its potential as a prognostic biomarker for glioma.