Identification of Critical m6A RNA Methylation Regulators with Prognostic Value in Lower-Grade Glioma

Abstract

Increasing evidences have revealed that N6-methyladenosine (m6A) RNA methylation regulators participate in the tumorigenesis and development of multiple tumors. So far, there has been little comprehension about the effects of m6A RNA methylation regulators on lower-grade gliomas (LGG). Here, we systematically investigated the expression profiles and prognostic significance of 36 m6A RNA methylation regulators in LGG patients from the TCGA and CGGA databases. Most of the m6A RNA methylation regulators are differentially expressed in LGG tissues as compared with normal brain tissues and glioblastoma (GBM) tissues. The consensus clustering for these m6A RNA methylation regulators identified three clusters. Patients in cluster 3 exhibited worse prognosis. In addition, we constructed an m6A-related prognostic signature, which exhibited excellent performance in prognostic stratification of LGG patients according to the results of the Kaplan-Meier curves, ROC curves, and univariate and multivariate Cox regression analyses. In addition, a significant correlation was observed between the m6A-related prognostic signature and the immune landscape of the LGG microenvironment. The high-risk group exhibited higher immune scores, stromal scores, and ESTIMATE scores but lower tumor purity and lower abundance of activated NK cells. Moreover, the expression level of immune checkpoints was positively correlated with the risk score. To conclude, the current research systematically demonstrated the prognostic roles of m6A RNA methylation regulators in LGG.

Single cell RNA sequencing reveals differentiation related genes with drawing implications in predicting prognosis and immunotherapy response in gliomas

“…In the training cohort, the AUC of our model for predicting 1-year and 2-year overall survival were higher than other models (F i g. 5 I). In addition, the accuracy of our model was also better than other glioma related models in the validation cohort 4 , 6 , 7 , 26 (Fig. 5 J).…”

Roles of the m6A Modification of RNA in the Glioblastoma Microenvironment as Revealed by Single-Cell Analyses

“…However, the effect of ICP blockades in GBM has not been satisfactory ( 42 ). Some studies have found that m 6 A modification was correlated with immune infiltration in glioma ( 43 – 47 ). However, to date, no research has analyzed the relationship between m 6 A modification and ICPs in GBM.…”

N6-Methyladenosine RNA Modification in the Tumor Immune Microenvironment: Novel Implications for Immunotherapy

“…Immune cells can penetrate into the brain and form an immune microenvironment. m 6 A regulatory factors are involved in multiple biological processes of tumor progression ( 50 , 83 – 85 ). Therefore, clarifying the relationship between m 6 A regulatory factors and TME-infiltrating immune cells can help to assess the anticancer response to immunotherapy in glioblastoma patients ( 50 ).…”

“…The m 6 A modification regulator ELAVL1 was an effective predictor of PD-L1 treatment efficacy ( 83 ). Compared with normal brain tissues and glioblastoma tissues, most m 6 A RNA methylation regulators are differentially expressed in lower-grade gliomas tissues ( 85 ). Studies have revealed the correlation between TME infiltration of immune cells and m 6 A modification ( 86 ).…”