Abstract
BACKGROUND: The tumor microenvironment (TME) typically experiences oxidative stress (OS), marked by a high level of reactive oxygen species (ROS) that can impact tumor advancement and prognosis by modulating the behavior of tumor cells and various immune cells. Oxidative stress-related genes (OSRG) encompass a range of genes involved in ROS pathways, and their specific roles in breast cancer (BC) necessitate further investigation. METHODS: Univariate Cox analysis was performed on genes linked to the OS pathway in the Gene Set Enrichment Analysis (GSEA) database, leading to the identification of 29 significant OSRG in BC. OSRG was divided into three distinct clusters according to the expression and the OSRG score based on the differentially expressed genes (DEGs) was further calculated by principal component analysis (PCA). The correlation between OSRG score and BC clinical features, mutation characteristics, immune checkpoints and immune cell infiltration was analyzed. Establish a multiariable Cox regression model to predict OSRG score effects on clinical characteristics. RESULTS: Significant differences were observed in survival analysis, enriched pathways, and immune infiltration among the three OSRG clusters based on 29 genes. Gene clusters were identified through the final selected 395 DEGs, revealing three distinct OSRG expression patterns. An OSRG score model was constructed using DEGs, demonstrating a significant association between high OSRG score and poor prognosis. Significantly, immune checkpoint-related genes exhibited a notable upregulation in the high OSRG score cohort. Additionally, a positive correlation was observed between the OSRG score and tumor mutation burden (TMB) in BC. The OSRG score holds potential implications for clinical immunotherapy in BC patients, and a nomogram was constructed with robust predictive capability for evaluating patient prognosis. CONCLUSIONS: This study elucidated the features of OSRG within BC TME and their possible prognostic significance, offering valuable insights for the development of more targeted immunotherapy approaches for individuals with BC.