Comprehensive analysis of m6A/m5C/m1A-related gene expression, immune infiltration, and sensitivity of antineoplastic drugs in glioma

Abstract

This research aims to develop a prognostic glioma marker based on m6A/m5C/m1A genes and investigate the potential role in the tumor immune microenvironment. Data for patients with glioma were downloaded from The Cancer Genome Atlas (TCGA) and Chinese Glioma Genome Atlas (CGGA). The expression of genes related to m6A/m5C/m1A was compared for normal and glioma groups. Gene Ontology and Kyoto Encyclopedia of Genes and Gene enrichment analysis of differentially expressed genes were conducted. Consistent clustering analysis was performed to obtain glioma subtypes and complete the survival analysis and immune analysis. Based on TCGA, Lasso regression analysis was used to obtain a prognostic model, and the CGGA database was used to validate the model. The model-based risk scores and the hub genes with the immune microenvironment, clinical features, and antitumor drug susceptibility were investigated. The clinical glioma tissues were collected to verify the expression of hub genes via immunohistochemistry. Twenty genes were differentially expressed, Consensus cluster analysis identified two molecular clusters. Overall survival was significantly higher in cluster 2 than in cluster 1. Immunological analysis revealed statistically significant differences in 26 immune cells and 17 immune functions between the two clusters. Enrichment analysis detected multiple meaningful pathways. We constructed a prognostic model that consists of WTAP, TRMT6, DNMT1, and DNMT3B. The high-risk and low-risk groups affected the survival prognosis and immune infiltration, which were related to grade, gender, age, and survival status. The prognostic value of the model was validated using another independent cohort CGGA. Clinical correlation and immune analysis revealed that four hub genes were associated with tumor grade, immune cells, and antitumor drug sensitivity, and WTAP was significantly associated with microsatellite instability(MSI). Immunohistochemistry confirmed the high expression of WTAP, DNMT1, and DNMT3B in tumor tissue, but the low expression of TRMT6. This study established a strong prognostic marker based on m6A/m5C/m1A methylation regulators, which can accurately predict the prognosis of patients with gliomas. m6A/m5C/m1A modification mode plays an important role in the tumor microenvironment, can provide valuable information for anti-tumor immunotherapy, and have a profound impact on the clinical characteristics.

Deciphering the Divergent Gene Expression Landscapes of m6A/m5C/m1A Methylation Regulators in Hepatocellular Carcinoma Through Single-Cell and Bulk RNA Transcriptomic Analysis

“…The purpose of this data collection was to assess the expression levels of m6A/m5C/m1A genes in HCC. Based on previously published literature, 5,30,32,37,38,[42][43][44] 35 m6A, 16 m5C, and 13 m1A regulator genes were selected (Table S1). The FPKM data were first transformed into transcripts per million and normalized.…”

“…Several studies have demonstrated the importance of the m6A, m1A, and m5C regulatory genes in RNA modifications [31][32][33][34][35][36][37][38] and cancer progression. 30,[38][39][40] To regulate methylation, writers modify DNA through various chemical changes, such as methyl group moieties. These molecular decorations can then attract several proteins known as "readers" that identify these moieties.…”

Mass Spectrometry-Based Pipeline for Identifying RNA Modifications Involved in a Functional Process: Application to Cancer Cell Adaptation

“…To illustrate this principle, our group has recently uncovered “epitranscriptomic signatures” from glioma patients’ cohorts that could be exploited to guide glioma/glioblastoma diagnosis with unmet accuracy . Far from being mere passengers in the tumorigenic process, several of these marks participate in cancer adaptation to conventional treatments and inhospitable environment. − For instance, recent reports show that a dysregulation of 5-methylcytidine (m 5 C) players is associated with either oncogenic or tumor-suppressive functions according to cellular context. , The identification of RNA marks driving cancer cell adaptation to inhospitable environment and conventional treatment is essential to design appropriate therapeutic strategies, as emphasized by a growing drug discovery effort in the field . Yet, the use of sequencing data is unsuitable for this purpose, as the regulation of these marks is subject to various post-transcriptional parameters, some of which are inherent to any subcellular enzymatic system. , Target(s) discovery steps necessitate the implementation of a dedicated pipeline that would allow the accurate quantification of RNA marks on isolated RNA species.…”

Characterization of the m6A/m1A/m5C/m7G‐related regulators on the prognosis and immune microenvironment of glioma by integrated analysis of scRNA‐seq and bulk RNA‐seq data

“…Regretably, most studies only focus on one type of RNA modification, but ignore the potential synergistic effects of different RNA modifications on the prognosis of gliomas. Although one study 19 established a prognostic model based on m6A/m5C/m1A‐related regulators, the m7G regulators were not integrated. The potential role of m6A/m1A/m5C/m7G‐related regulators in the tumor microenvironment (TME) and prognosis for glioma patients remains unclear.…”