Identification of an N6-methyladenosine (m6A)-related signature associated with clinical prognosis, immune response, and chemotherapy in primary glioblastomas

Background: N6-methyladenosine (m6A) RNA methylation regulators play crucial role in tumorigenicity and progression. However, their biological significance in primary glioblastomas (GBM) has not been fully elucidated. Methods: In the present study, we evaluated the 22 m6A RNA regulators using the integrated data of primary GBM samples from The Cancer Genome Atlas and Chinese Glioma Genome Atlas databases. The different m6A modification patterns and m6A-related gene signature in primary GBM were distinguished by using principal component analysis. Single-sample gene set enrichment analysis was introduced to assess the relative level of immune infiltration. Gene set variation analysis was performed to calculate the enrichment score of the signaling pathways for different clusters. An m6A scoring scheme was established to evaluate the m6A modification pattern in individual tumors in order to predict prognosis and evaluate tumor microenvironment (TME) cell infiltration, immune response, and chemotherapy effect in primary GBM. Results: Two distinct m6A modification subgroups associated with different clinical features and biological pathways were identified among the 371 primary GBM. Based on 132 prognostic m6A phenotype-related differentially expressed genes (DEGs) between 2 m6A cluster subgroups, an m6A scoring model was constructed to assess the m6A modification pattern in individual tumors. The high-m6A score group was associated with better prognosis and immune response and worse chemotherapy effect. Conclusions: The findings of the present study indicate the potential role of m6A modification in primary GBM, which will help enhance our understanding of TME characteristics, predict clinical prognosis, and provide important insight into effective immunotherapy and chemotherapy.