High expression of CCNB2 is an independent predictive poor prognostic biomarker and correlates with immune infiltrates in breast carcinoma.

ABSTRACT

Background: Cyclin B2 (CCNB2) is associated with cell cycle progression, acting as a cell cycle checkpoint in progression of G2/M transition. In many cancer patients, it has been observed that overexpression of CCNB2 enhances tumor invasiveness and leads to adverse prognosis. However, the association of CCNB2 with the tumor microenvironment remains unclear. Therefore, it is necessary to clarify the associations of CCNB2 with the immune status and prognosis of breast carcinoma (BRCA). Methods: Gene expression and clinical data for BRCA were obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases, followed by association analyses of CCNB2 expression with prognosis, immune cell infiltration, and immune checkpoints. This study further performed drug sensitivity analysis and constructed a prognostic nomogram for CCNB2. Results: 3619 differentially expressed genes were identified in BRCA, including CCNB2 that emerged as a key gene in the network. High CCNB2 expression correlated with poor prognosis. Functional analysis demonstrated enrichment of CCNB2 co-expressed genes with the cell cycle, cancer progression, cell energy, and immune pathways. Microsatellite instability and tumor mutation burden analyses indicated CCNB2 as a candidate immunotherapy target. Tumor-infiltrating myeloid-derived suppressor cells, regulatory T cells, and T helper 2 cells were associated with CCNB2-related tumor progression and metastasis. CCNB2 expression positively correlated with immune checkpoints, indicating that high CCNB2 expression might facilitate tumor immune escape. Tumors with high CCNB2 expression showed sensitivity to phosphoinositide 3-kinase-protein kinase B-mammalian target of rapamycin and cyclin-dependent kinase (CDK) 4/6 inhibitors, and the nomogram had good prognostic predictive ability for patients with BRCA. Conclusions: CCNB2 may play a crucial role in tumorigenesis and serve as an independent prognostic biomarker associated with tumor microenvironment, tumor immune infiltration and immunotherapy in BRCA.