Development of a risk model to predict prognosis in breast cancer based on cGAS-STING-related genes

Abstract

Background: Breast cancer (BRCA) is regarded as a lethal and aggressive cancer with increasing morbidity and mortality worldwide. cGAS-STING signaling regulates the crosstalk between tumor cells and immune cells in the tumor microenvironment (TME), emerging as an important DNA-damage mechanism. However, cGAS-STING-related genes (CSRGs) have rarely been investigated for their prognostic value in breast cancer patients.Methods: Our study aimed to construct a risk model to predict the survival and prognosis of breast cancer patients. We obtained 1087 breast cancer samples and 179 normal breast tissue samples from the Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEX) database, 35 immune-related differentially expression genes (DEGs) from cGAS-STING-related genes were systematically assessed. The Cox regression was applied for further selection, and 11 prognostic-related DEGs were used to develop a machine learning-based risk assessment and prognostic model.Results: We successfully developed a risk model to predict the prognostic value of breast cancer patients and its performance acquired effective validation. The results derived from Kaplan-Meier analysis revealed that the low-risk score patients had better overall survival (OS). The nomogram that integrated the risk score and clinical information was established and had good validity in predicting the overall survival of breast cancer patients. Significant correlations were observed between the risk score and tumor-infiltrating immune cells, immune checkpoints and the response to immunotherapy. The cGAS-STING-related genes risk score was also relevant to a series of clinic prognostic indicators such as tumor staging, molecular subtype, tumor recurrence, and drug therapeutic sensibility in breast cancer patients.Conclusion: cGAS-STING-related genes risk model provides a new credible risk stratification method to improve the clinical prognostic assessment for breast cancer.