Immune Landscape in PTEN-Related Glioma Microenvironment: A Bioinformatic Analysis

Introduction: PTEN gene mutations are frequently found in the genetic landscape of high-grade gliomas since they influence cell proliferation, proangiogenetic pathways, and antitumoral immune response. The present bioinformatics analysis explores the PTEN gene expression profile in HGGs as a prognostic factor for survival, especially focusing on the related immune microenvironment. The effects of PTEN mutation on the susceptibility to conventional chemotherapy were also investigated. Methods: Clinical and genetic data of GBMs and normal tissue samples were acquired from The Cancer Genome Atlas (TCGA)-GBM and Genotype-Tissue Expression (GTEx) online databases, respectively. The genetic differential expressions were analyzed in both groups via the one-way ANOVA test. Kaplan-Meier survival curves were applied to estimate the overall survival (OS) and disease-free survival (DFS). The Genomics of Drug Sensitivity in Cancer platform was chosen to assess the response of PTEN-mutated GBMs to temozolomide (TMZ). p < 0.05 was fixed as statistically significant. On Tumor Immune Estimation Resource and Gene Expression Profiling Interactive Analysis databases, the linkage between immune cell recruitment and PTEN status was assessed through Spearman's correlation analysis. Results: PTEN was found mutated in 22.2% of the 617 TCGA-GBMs patients, with a higher log2-transcriptome per million reads compared to the GTEx group (255 samples). Survival curves revealed a worse OS and DFS, albeit not significant, for the high-PTEN profile GBMs. Spearman's analysis of immune cells demonstrated a strong positive correlation between the PTEN status and infiltration of T-reg (rho = 0.179) and M2 macrophages (rho = 0.303). The half-maximal inhibitor concentration of TMZ was proven to be lower for PTEN-mutated GBMs compared with PTEN wild-types. Conclusions: PTEN gene mutations prevail in GBMs and are strongly related to poor prognosis and least survival. The infiltrating immune lymphocytes T-reg and M2 macrophages populate the glioma microenvironment and control the mechanisms of tumor progression, immune escape, and sensitivity to standard chemotherapy. Broader studies are required to confirm these findings and turn them into new therapeutic perspectives.

Automated summary

PTEN gene mutations are frequently found in high-grade gliomas and are strongly associated with poor prognosis and lower survival rates. PTEN wild-type gliomas exhibit lower sensitivity to chemotherapy compared to PTEN-mutated gliomas. In addition, there is a strong positive correlation between PTEN status and the infiltration of T-reg and M2 macrophages. These findings highlight the importance of PTEN gene in high-grade gliomas and provide potential clues for new therapeutic strategies.