Development and Validation of a Novel Prognostic Model for Lower-Grade Glioma Based on the m6A-regulated Genes

Abstract

Abstract Background: Methylation of N6-methylandenosine (m6A) has important roles in the growth of tumors and cellular biological processes. The immune system is involved in tumourigenesis and development, and plays a certain role in tumour therapy and in resistance to drugs. There have been no in-depth studies on m6A-related immune markers in Low Grade Glioma (LGG). Methods: LGG patients' mutation data and gene expression and related clinical information were obtained from the China Glioma Genome Atlas (CGGA) database and The Cancer Genome Atlas (TCGA). The prognostic model was calculated using multivariate Cox, LASSO, univariate Cox and other analytical approaches. All data was classified by two-cluster typing. Finally, we determined the biological role of FBXO4 in glioma cells by quantitative reverse transcription-polymerase chain reaction, cell proliferation assay and cell migration assay. Results: The prognostic model for LGG worked well. It has an area under the curve over 0.9. The survival curve for the cluster typing and the Sankey diagram showed that high m6A levels corresponded to high expression of m6A regulatory genes and immune genes, and were associated with a higher degree of immune infiltration and lower survival rates. Finally, silencing FBXO4in glioma cell lines can significantly inhibit their proliferation and migration ability. Conclusion: Prognostic models can accurately and efficiently help investigators analysis the prognosis of LGG patients. And the correlation analysis between m6Ascore and tumor microenvironment can provide a basis for further exploratio. Finally, FBXO4 is an important biomarker for the diagnosis and prognosis of Low Grade Glioma.