The prognostic role of p53 and its correlation with CDK9 in urothelial carcinoma.

ABSTRACT

PURPOSE: The mutation of p53 is considered a pivotal step in bladder cancer pathogenesis. Recently, distinct interactions between p53 and CDK9, a transcription regulator, have been described. In this work, we explored the prognostic role of p53 expression and evaluated its associations with CDK9 in urothelial carcinoma. MATERIALS AND METHODS: The research group consisted of 67 bladder cancer samples and 32 normal urothelial mucosa samples. All specimens were analyzed using ImageJ and the IHC profiler plugin. To validate the results, 406 cases from The Cancer Genome Atlas database were analyzed. RESULTS: P53 and CDK9 are overexpressed in urothelial cancer tissues when compared to normal urothelial tissues (p < 0.05). High p53 expression was observed in metastatic tumors and tumors with high CDK9 expression (p < 0,05). High p53 expression was predictive for shorter survival in patients with non-muscle-invasive bladder cancer (HR = 0.107 [0.012-0.96]; p = 0.046) but did not correlate with prognosis in the muscle-invasive group. In high CDK9 cancers, high p53 expression correlated with the occurrence of high-grade and muscle-invasive tumors (p < 0.05). CONCLUSION: High expression of p53 correlates with unfavorable clinical features of bladder cancer. CDK9 is associated with the expression of p53, possibly through interactions with p53 inhibitors. Since the blockade of CDK9 in other malignancies reactivates wild-p53 activity, confirming the crosstalk between p53 and CDK9 in bladder cancer may be another step to explain the mechanism of tumor progression in its early stages.