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

Abstract

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.