Aging microenvironment: the critical factor to determine the prognosis of glioblastoma from the perspective of response to chemoradiotherapy and immunoregulation

Glioblastoma (GBM) is a highly aggressive brain tumor. With age, many factors in the microenvironment will change, and these changes have an important impact on tumor growth, development and treatment response. This study aims to investigate gene signatures and prognostic value of the aging microenvironment in GBM. The correlation between transcriptional data, clinical information, immune infiltration, and expression of inflammatory cytokines was analyzed. A protein-protein interaction network (PPI) and functional enrichment analysis was performed. The correlation between survival data and prognosis was evaluated by Cox regression analysis to predict the response to treatment. Most aging-related gene sets were significantly concentrated and 437 aging-related hub genes were highly expressed in GBM samples. Among 437 hub genes, the expression of 49 genes was significantly correlated with prognosis. The mutation rate of the top 20 aging-related hub genes in the GBM sample was 51.4%. Functional enrichment analysis revealed that most aging-related hub genes with significant survival correlation may be involved in regulating immunotherapy response. The aging microenvironment-related signature (AMRS) was identified as a independent prognostic indicator and correlated with clinical features, immunity, and inflammation in GBM. The aging microenvironment is involved in the mechanism of GBM drug resistance which showed great potential for further studing of new avenues for clinical treatment to improve patients’ outcomes.