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

N5-methylcytosine (mC) 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 mC modification in glioma patients. Initially, we identified two distinct mC clusters based on the expression level of mC regulators in The Cancer Genome Atlas glioblastoma (TCGA-GBM) dataset. Differentially expressed genes (DEGs) between the two mC cluster groups were determined. Utilizing these mC regulation-related DEGs, we classified glioma patients into three gene cluster groups: A, B, and C. Subsequently, an mC scoring system was developed through a univariate Cox regression model, quantifying the mC 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 mC scores. In test (TCGA-GBM) and validation (Chinese Glioma Genome Atlas [CGGA]-1018 and CGGA-301) datasets, glioma patients with a higher mC 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 mC cluster groups and risk groups. Our study developed a novel prognostic scoring system based on mC modification patterns for glioma patients, complementing existing molecular classifications and providing valuable insights into prognosis for glioma patients.