A novel prognostic risk-scoring system based on m⁵C methylation regulator-mediated patterns for glioma patients

N5-methylcytosine (m⁵C) methylation modification plays a crucial role in the epigenetic mechanisms underlying tumorigenesis, aggressiveness, and malignancy in diffuse glioma. Our study aimed to develop a novel prognostic risk-scoring system to assess the impact of m⁵C modification in glioma patients. Initially, we identified two distinct m⁵C clusters based on the expression level of m⁵C regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two m⁵C cluster groups were determined. Utilizing these m⁵C regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an m⁵C scoring system was developed through a univariate Cox regression model, quantifying the m⁵C modification patterns utilizing six DEGs associated with disease prognosis. The resulting scoring system allowed us to categorize patients into high- or low-risk groups based on their m⁵C scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher m⁵C score consistently exhibited shorter survival durations, fewer isocitrate dehydrogenase (IDH) mutations, less 1p/19q codeletion and higher World Health Organization (WHO) grades. Additionally, distinct immune cell infiltration characteristics were observed among different m⁵C cluster groups and risk groups. Our study developed a novel prognostic scoring system based on m⁵C modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.