Integrated analysis of cell cycle-related genes in HR+/HER2- breast cancer.

ABSTRACT

PURPOSE: This study aimed to explore the mutational characteristics and significance of cell cycle-related genes (CCGs) in hormone-receptor positive, human epidermal growth factor receptor 2 negative breast cancer (HR+/HER2- BC). METHODS: A total of 1668 HR+/HER2- BC patients from the Guangdong Provincial People's Hospital (GDPH) cohort (n = 321) and METABRIC cohort (n = 1347) were included. Tumor samples from HR+/HER2- BC patients were collected for a next-generation sequencing assay in GDPH cohort, including 15 key CCGs. The association between CCGs alterations and overall survival were identified via the Cox regression analysis. The functional roles of the CCGs were explored via the Metascape database. RESULTS: Based on multivariate Cox regression analysis, a set of five key CCGs (CDK4, CCND1, CDKN1A, CDKN1C, and CHEK2) were identified as independent prognostic variables in HR+/HER2- BC patients. Besides, the five-CCGs-based risk score was used to effectively classify patients into the low-risk and high-risk groups (P < 0.0001). The potential functional pathways of the CCGs included cell cycle, cyclin D associated events in G1, and regulation of G1/S transition of mitotic cell cycle. CONCLUSION: We performed the integrated analysis of the CCGs in HR+/HER2- BC patients. It has the potential to guide individualized precision oncology therapeutic schemes in HR+/HER2- BC patients.