A circadian rhythm-related gene signature for prognosis, invasion and immune microenvironment of breast cancer

Abstract

Background: Circadian dysregulation is linked to the onset and progression of cancer, but current knowledge of the role of circadian rhythm-related genes (CRRGs) in breast cancer (BC) is limited and incomplete. The purpose of this study was to investigate the potential role and immune-related prognostic significance of CRRGs in BC. Methods: The Cancer Genome Atlas breast cancer (TCGA-BRCA) genetic data were combined with 1369 CRRGs to create a model of BC prognosis-related CRRGs. To validate the model’s predictive power in TCGA and other external datasets, the Kaplan-Meier survival curve and receptor operation characteristic curve were plotted. The relationship between CRRGs model and gene enrichment pathways, immune cell infiltration, and differences in patient response to immune checkpoint inhibitors (ICIs) therapy was then discussed. Results: A CRRG-based eighteen-gene model was developed that accurately predicted the survival time of BC patients. Based on this model, BC patients can be classified as high or low risk. The high-risk group has negative immune cell infiltration (such as macrophages M0 and M2) and a poor therapeutic response to ICIs due to lower immune checkpoint gene expression. Furthermore, TCF7 and IFNG were found to be strongly associated with immune checkpoints in CRRGs model. Conclusion: The 18 CRRGs may be useful in assessing the prognosis of BC patients, studying immune infiltration, and developing more effective immunotherapy strategies.