The Role of m5C-Related lncRNAs in Predicting Overall Prognosis and Regulating the Lower Grade Glioma Microenvironment

Abstract

Glioma is the most lethal primary brain tumor with a poor prognosis and high recurrence rate. Enormous efforts have been made to find therapeutic targets for gliomas. In the current study, we identified m5C-related lncRNAs through Pearson correlation analysis by the criteria |R|>0.5 and p<0.001 in TCGA LGG and CGGA325 datasets. We then established an eight-lncRNA m5C-related prognostic signature (m5C LPS) through lasso cox regression analysis and multivariate analysis. The performance of the signature was confirmed in the CGGA325 dataset and evaluated in differential subgroups divided by relevant clinicopathological characteristics. Patients were then divided into high and low risk groups using risk scores calculated with the signature. Next, we performed GO, KEGG and gene set enrichment analysis (GSEA) and identified the m5C LPS to be related with glioma microenvironment, immune response, EMT, cell cycle, and hypoxia. Correlation of the risk groups with immune cell infiltration, somatic mutation, and CNVs was then explored. Responses to immuno- and chemotherapies in different risk groups were evaluated using submap and pRRophetic R packages respectively. The high-risk group was more sensitive to anti-CTLA4 therapy and to compounds including Temozolomide, Bleomycin, Cisplatin, Cyclopamine, A.443654 (Akt inhibitor), AZD6482 (PI3K inhibitor), GDC0941(PI3K inhibitor), and metformin. We present for the first time a m5C-related lncRNA signature for lower grade glioma patient prognosis and therapy response prediction with validated performance, providing a promising target for future research.