Prognostic Value and Immunogenomic Analysis of a Signature Derived from Immune Cell Infiltration in Glioblastoma

Abstract

Background: Glioblastoma (GBM) is the most prevalent primary malignant brain tumor. However, current prognostic indicators do not accurately predict the prognostic and therapeutic benefits of GBM patients, therefore we proposed a new immune-based classification of GBM and find out patients more sensitive to immunotherapy. Methods: This study established a novel immune-based classification, the immune-related prognostic score (IRPS), by utilizing four GBM cohorts comprising 302 samples. Furthermore, a comprehensive immunogenomic analysis was conducted to assess the relationship between IRPS and clinical prognosis, immune cell infiltration, immune checkpoints, and potential mechanisms of immune evasion. The Chinese Glioma Genome Atlas (CGGA) GBM cohort was also used to validate the IRPS. The findings of this research demonstrate the potential of IRPS as a biomarker for predicting the overall survival (OS) of GBM patients. Additionally, the analysis of Tumor Immune Dysfunction and Exclusion (TIDE) and mRNA stemness index (mRNAsi) has suggested that patients with high IRPS may exhibit increased responsiveness to immunotherapy. Results: The patients were ranked according to the IRPS score and stratified into high and low IRPS groups. Kaplan-Meier survival analysis revealed a significant difference in prognosis within the two subgroups in both the training and testing datasets. The results showed that the low IRPS subgroup higher degree of immune cell infiltration compared to those of the high IRPS subtype. Tumors in the low IRPS group may express more immune checkpoint molecules as a means of evading immune killing following immune stimulation. In the high IRPS subtype of GBM, TP53 (49%) was the most frequently mutated gene, while in the low IRPS subtype, only 31% showed this mutation. Moreover, the high IRPS subtype GBM is also more susceptible to mut-p53 therapy degradation compared to GBM of the low IRPS subtype. Additionally, the analysis of TIDE and mRNAsi has suggested that patients with high IRPS may exhibit increased responsiveness to immunotherapy. Conclusions: These findings suggest that IRPS could function as a reliable prognostic biomarker, facilitate the development of novel immunotherapeutic interventions, and assist in clinical decision-making for GBM patients.