N7-methylguanosin regulators-mediated methylation modification patterns and characterization of the immune microenvironment in lower-grade glioma

Abstract

N7-methylguanosine (m7G) modification signature has recently emerged as a crucial regulator of tumor progression and treatment in cancer. However, there is limited information available on the genomic profile of lower-grade gliomas (LGGs) related to m7G methylation modification genes’ function in tumorigenesis and progression. In this study, we employed bioinformatics methods to characterize m7G modifications in individuals with LGG from The Chinese Glioma Genome Atlas (CGGA) and The Cancer Genome Atlas (TCGA). We used gene set enrichment analysis (GSEA), single sample GSEA (ssGSEA), CIBERSORT algorithm, ESTIMATE algorithm, and TIDE to evaluate the association between m7G modification patterns, tumor microenvironment (TME) cell infiltration properties, and immune infiltration markers. The m7G scoring scheme using principal component analysis (PCA) was employed to investigate the m7G modification patterns quantitatively. We examined the m7G modification hub genes' expression levels in normal samples, refractory epilepsy samples, and LGG samples using immunohistochemistry, western-blotting, and qRT-PCR. Our findings revealed that individuals with LGG could be categorized into two groups based on m7G scores (high and low) according to the properties of m7G. Moreover, we observed that high m7G score was associated with significant clinical benefit and prolonged survival duration in the anti-PD-1 cohort, while low m7G score was associated with improved prognostic outcomes and increased likelihood of complete or partial response in the anti-PD-L1 cohort. Different m7G subtypes also showed varying Tumor Mutational Burden (TMB) and immune profiles and might have distinct responses to immunotherapy. Furthermore, we identified five potential genetic markers that were highly correlated with the m7G score signature index. These findings provide insight into the features and classification associated with m7G methylation modifications and may aid in improving the clinical outcome of LGG.

Predicting the risk of primary Sjögren's syndrome with key N7-methylguanosine-related genes: A novel XGBoost model

“…EIF4E has been demonstrated to participate in the translation of viral mRNA and the proliferation of infected cells [ 49 ]. SARS-CoV-2 can effectively replicate in target cells by utilizing the ERK/MNK1/EIF4E pathway [ 50 , 51 ]. Extensive research has found that EIF4E2 plays a crucial role in tumor progression and metastasis [ 52 ].…”

M7G-related tumor immunity: novel insights of RNA modification and potential therapeutic targets

“…Meanwhile, PD-1 and CTLA-4 were overexpressed as well [133,138]. Analogous studies in GC, CRC and lower-grade glioma (LGG) showed the overexpression of PD-L1 in patients with high m7G level [105,145,146], and the other immune checkpoint of tumor cells, CD276 showed same outcomes [147]. Consequently, m7G modification emerged as a predictive factor for the immunological response to anti-PD-L1 therapy [116,146].…”

“…Analogous studies in GC, CRC and lower-grade glioma (LGG) showed the overexpression of PD-L1 in patients with high m7G level [105,145,146], and the other immune checkpoint of tumor cells, CD276 showed same outcomes [147]. Consequently, m7G modification emerged as a predictive factor for the immunological response to anti-PD-L1 therapy [116,146]. These findings underscored the influence of m7G modification on the expression of immune checkpoints in tumor cells, positioning it as a potential biomarker or therapeutic target for immunotherapy.…”

“…For the concrete ICB therapy strategies, researchers examined the predictive value of m7G signature in different immunotherapy cohorts. According to the anti-PD-1 and anti-PD-L1 immunotherapy cohorts, low-risk group of patients in HCC, SKM, LGG and bladder cancers showed significant clinical benefits for anti-PD-1 or anti-PD-L1 treatment 115 , 116 , 146 , 170 . However, the scenario is nuanced when considering combination therapy.…”

Insights into the regulatory role of RNA methylation modifications in glioma

“…This regulatory mechanism plays significant roles in cell fate, proliferation, metabolism, and pathological processes. Given their importance, a deeper understanding of the role of epitranscriptomic modifications in the pathogenesis of tumors, including gliomas, is critical for the development of novel diagnostic and therapeutic approaches [6][7][8][9]. Epigenetics is a complex process involving various modifications such as histone modification, chromatin remodeling, nucleosome localization, DNA methylation, and RNA modification.…”