A Circadian Rhythm-related Signature to Predict Prognosis, Immune Infiltration, and Drug Response in Breast Cancer

Purpose: Circadian rhythm-related genes (CRRGs) play essential roles in cancer occurrence and development. However, the prognostic significance of CRRGs in breast cancer (BC) has not been fully elucidated. Our study aimed to develop a prognostic gene signature based on CRRGs that can accurately and stably predict the prognosis of BC. Methods: The transcriptome data and clinical information for BC patients were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A consensus unsupervised clustering analysis was carried out to investigate the roles of CRRGs in BC. A CRRGs-related prognostic risk model was established by using logistic least absolute shrinkage and selection operator (LASSO) Cox regression and univariate Cox regression analyses. Kaplan-Meier (KM) curves analysis, time-dependent receptor operation characteristics (ROC) curves analysis, and nomogram were plotted to evaluate the predictive efficacy of the model. The relevance of risk score to the immune cell infiltration, tumor burden mutation (TMB), and therapeutic response was assessed. Results: risk model comprising six CRRGs (SLC44A4, SLC16A6, TPRG1, FABP7, GLYATL2, and FDCSP) was constructed and validated, demonstrating an effective predictor for the prognosis of BC. The low-risk group displayed a higher expression of immune checkpoint genes and a lower burden of tumor mutation. Additionally, drug sensitivity analysis demonstrated that the prognostic signature may serve as a potential chemosensitivity predictor. Conclusion: We established 6 CRRGs-related risk signatures for the prognosis of BC, which is of great value in predicting the prognosis of patients with BC and guiding the treatment for BC.