BUB1-based risk model predicts prostate cancer prognosis and reveals therapeutic vulnerabilities

Mitosis serine/threonine-protein kinase BUB1 is an anoikis-related gene that may be inversely related to tumor progression due to its role in programmed cell death. We aimed to develop a risk and prognosis prediction model for the BUB1 gene after in vitro validation and find potential targeted drugs for prostate cancer (PCA).

The prediction model was established using univariate Cox, multivariate Cox, and LASSO regression. Receiver operating characteristic curves determined the predictive performance, and the GEO database was used for external validation. Patients' prognoses were compared using Kaplan-Meier analysis. We investigated immune cell infiltration and sensitivity to immunotherapeutic drugs in PCA patients. Cell experiments illustrated the influence of BUB1 on cell invasiveness, viability, and epithelial-mesenchymal transition (EMT).

BUB1-based four-gene prediction model divided patients into low- and high-risk group. Patients in the high-risk group had worse overall survival than those in the low-risk group, with significant differences in immune cell infiltration, immune checkpoint expression, and sensitivity to immunotherapeutic drugs. Drug sensitivity illustrated that over ten drugs may be effective for higher risk patients. Knocking down the BUB1 gene in PC3 and C4-2 cell lines reduced PCA cell proliferation and invasion and altered EMT-related protein expression.

After external validation, a BUB1-based four-gene prognostic signature, which may represent a subtype of PCA with more aggressive and metastatic characteristics, was shown to accurately predict the prognosis of PCA. In vitro experiments revealed that the BUB1 gene significantly affects the proliferation, invasion, and expression of specific EMT-related proteins in PCA cells.