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

ABSTRACT: Glioblastoma (GBM) is a group of intracranial neoplasms with intra-tumoral heterogeneity. RNA N6-methyladenosine (m⁶A) methylation modification reportedly plays roles in immune response. The relationship between the m⁶A modification pattern and immune cell infiltration in GBM remains unknown. Utilizing expression data of GBM patients, we thoroughly explored the potential m⁶A modification pattern and m⁶A-related signatures based on 21 regulators. Thereafter, the m⁶A 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 m⁶A modification characteristics. Based on differentially expressed genes (DEGs) within two clusters, m⁶A-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 m⁶A regulators and specific immune cell infiltration was demonstrated in our study and the m⁶A regulator ELAVL1 was determined to play an important role in the anticancer response to PD-L1 therapy. Our findings indicated the relationship between m⁶A 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 m⁶A-related signatures.

SUBMITTER: Pan Y 

PROVIDER: S-EPMC7947873 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature