Uncovering N7-Methylguanosine regulator-mediated methylation modification pattern and Landscape of anti-PD-1/L1 Immunotherapy and immune microenvironment infiltration characterization in Lower-Grade Glioma

Abstract

Abstract Background: N7-methylguanosine (m7G) modification signature has been found recently in cancer and is now known as an essential regulator of tumor progression and treatment. As a result of the function of m7G methylation modification genes in tumorigenesis and progression, there isn't much information related to the genomic profile of lower-grade gliomas(LGGs). Methods: In this research, bioinformatics analysis methods were used to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas(CGGA) and The Cancer Genome Atlas(TCGA). Afterward, gene set enrichment analysis(GSEA), single sample GSEA(ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, R package "GSVA," and TIDE were used to evaluate the association between m7G modification patterns, TME cell infiltration properties as well as the correlation regarding immune infiltration markers. The m7G scoring scheme using principal component analysis(PCA) was employed to investigate the m7G modification patterns of individual tumors quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and lower-grade glioma samples using immunohistochemistry, western-blotting, and QRT-PCR. Result: It was discovered that individuals with LGG were categorized into two groups in terms of m7G scores (high and low) as per the properties of m7G. After observing the anti-PD-1 cohort, it has been noted that individuals having a high m7G score had significant clinical benefit, along with considerably prolonged survival duration. Opposing this, individuals in the anti-PD-L1 cohort having low m7G scores had improved prognostic outcomes and were more likely to have CR(Complete Response) / PR(Partial Response). Different m7G subtypes have different TMB(Tumor Mutational Burden) and immune profiles and might have varied responses to immunotherapy. Moreover, five potential genetic markers were found that were highly correlated with the index of the m7G score signature. Conclusion: Conclusively, a thorough investigation of the features and classification associated with m7G methylation modifications may improve the clinical outcome of LGG.