Bioinformatics analysis and experimental validation reveal that CDC20 overexpression promotes bladder cancer progression and potential underlying mechanisms

Abstract

Background: Bladder cancer is a prevalent malignancy. CDC20, a pivotal cell cycle regulator gene, plays a significant role in tumour cell proliferation, but its role in bladder cancer remains unclear.

Objective: This study aimed to analyse CDC20 expression in bladder cancer and explore its roles in tumour progression, treatment response, patient prognosis, and cellular proliferation mechanisms.

Methods: We systematically analysed CDC20 expression in bladder cancer using bioinformatics. Our study investigated the impact of CDC20 on chemotherapy and radiotherapy sensitivity, patient prognosis, and changes in CDC20 methylation levels. We also explored the role and potential underlying mechanisms of CDC20 in bladder cancer cell growth. We used lentiviral transfection to downregulate CDC20 expression in 5637 and T24 cells, followed by CCK-8, colony formation, scratch, invasion, apoptosis, and cell cycle analyses.

Results: CDC20 is highly expressed in bladder cancer and is significantly correlated with poor prognosis. Moreover, CDC20 demonstrated high diagnostic potential for bladder cancer (AUC > 0.9). The tumour methylation levels of CDC20 in tumour tissues markedly decreased compared with those in normal tissues, and lower methylation levels were associated with a worse prognosis. Elevated CDC20 expression is linked to increased mutation burden. Our findings suggested a potential association between high CDC20 expression and resistance to chemotherapy and radiotherapy, as CDC20 expression may impact immune cell infiltration levels. Mechanistic analysis revealed the influence of CDC20 on bladder cancer cell proliferation through cell cycle-related pathways. According to the cell experiments, CDC20 downregulation significantly impedes bladder cancer cell proliferation and invasion, leading to G1 phase arrest.

Conclusion: Aberrantly high CDC20 expression promotes tumour progression in bladder cancer, resulting in a poor prognosis, and may also constitute a promising therapeutic target.

Keywords: Bladder cancer; CDC20; Cell cycle; Prognosis; Proliferation; Therapeutic target.