Construction of an m5Cscore based on m5C modification patterns to predict prognosis and personalized treatment outcomes in breast cancer

Abstract

Accumulating evidence links 5-methylcytosine (m 5 C) modifications to tumor progression and gene regulation. This study aimed to systematically characterize m 5 C modification patterns in breast cancer, elucidate their associations with prognosis and tumor heterogeneity, and provide references for prognostic stratification and immune microenvironment evaluation. We comprehensively profiled m 5 C regulator expression using multi-omics data from The Cancer Genome Atlas and Gene Expression Omnibus datasets. Unsupervised clustering was performed to identify distinct m 5 C modification subtypes. Meanwhile, we construct an m 5 Cscore to quantify the m 5 C modification patterns of individual samples. Correlations between the m 5 Cscore, tumor mutation burden, survival outcomes, and tumor immune microenvironment features were systematically evaluated. Distinct m 5 C modification subtypes (m 5 C cluster A and B) exhibiting significant prognostic differences were identified. m 5 C cluster A displayed elevated cell cycle activation, abundant activated T/B cell infiltration, high PD-1/PD-L1 expression, and inferior overall survival, whereas m 5 C cluster B featured suppressed proliferative signaling, enriched mast cells and plasmacytoid dendritic cells, low immune checkpoint levels, and favorable prognosis. The m 5 Cscore demonstrated significant associations with tumor mutation burden and overall survival, with higher scores correlating with favorable survival trend. Importantly, distinct m 5 C modification patterns were characterized by divergent immune cell infiltration profiles and immune checkpoint expression, and the m 5 Cscore was correlated with the expression of immune checkpoints, tumor mutational burden, and immune-related scores, indicating m 5 C-mediated immunomodulatory effects. m 5 C modification patterns are associated with breast cancer prognosis and anti-tumor immunity. The m 5 Cscore may aid in prognostic stratification and immune-related evaluation.