Identification and Validation of RNA Methylation-Related Related Alternative Splicing Gene Signature for Low Grade Glioma to Predict Survival and Immune Landscapes

Abstract

Abstract Background Lower-grade glioma (LGG) is a crucial pathological type of Glioma. The present study aimed to explore multiple RNA methylation regulator-related AS events and investigate their prognostic values in LGG. Methods The prognostic model for Low-Grade Glioma was established by using the LASSO regression analysis. To validate prognostic value, we performed Kaplan-Maier survival analysis, ROC curves and nomograms. The ESTIMATE algorithm, the CIBERSORT algorithm and the ssGSEA algorithm were utilized to explore the role of the immune microenvironment in LGG. Subsequently, we then used GO, KEGG and GSEA enrichment analysis to explore the functional roles of these genes. In addition, we employed the GDSC database to screen potential chemotherapeutic agents. Results Eight RNA methylation related AS events were involved in construct a survival and prognosis model, which had good ability of independent prediction for patients with LGG. Patients in the high-risk group had shorter life expectancy and higher mortality, while patients in the low-risk group had a better prognosis. We constructed a nomogram which showed an excellent predictive performance for individual OS. The risk score exhibited a close correlation with some immune cells and expression of immune checkpoints. Patients in high-risk group were characterized by immunosuppressive microenvironment and poor response to immunotherapy, and were sensitive to more chemotherapeutic drugs. Pathway and functional enrichment analyses further confirmed that significant differences existed in immune landscape between the two subgroups. Conclusion The prognostic RNA Methylation-related Alternative Splicing signature we constructed could constitute a promising prognostic biomarker, which could serve to optimize treatment regimens.