RNA N6-Methyladenosine Regulator-Mediated Methylation Modifications Pattern and Immune Infiltration Features in Glioblastoma

胶质母细胞瘤中RNA N6-甲基腺苷调节因子介导的甲基化修饰模式和免疫浸润特征

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Abstract

Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m(6)A) methylation modification reportedly plays roles in immune response. The relationship between the m(6)A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m(6)A modification pattern and m(6)A-related signatures based on 21 regulators. Thereafter, the m(6)A methylation modification-based prognostic assessment pipeline (MPAP) was constructed to quantitatively assess GBM patients' clinical prognosis combining the Robustness and LASSO regression. Single-sample gene-set enrichment analysis (ssGSEA) was used to estimate the specific immune cell infiltration level. We identified two diverse clusters with diverse m(6)A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m(6)A-related signatures were identified to establish the MPAP, which can be used to quantitatively forecast the prognosis of GBM patients. In addition, the relationship between 21 m(6)A regulators and specific immune cell infiltration was demonstrated in our study and the m(6)A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m(6)A methylation modification patterns and tumor microenvironment immune cell infiltration, through which we could comprehensively understand resistance to multiple therapies in GBM, as well as accomplish precise risk stratification according to m(6)A-related signatures.

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