Published in:
01-01-2021 | Kidney Cancer | Original Article – Cancer Research
B-MYB—p53-related relevant regulator for the progression of clear cell renal cell carcinoma
Published in: Journal of Cancer Research and Clinical Oncology | Issue 1/2021
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Purpose
To investigate the mRNA expression of B-MYB and MDM2 together with their p53 relatedness in clear cell renal cell carcinoma (ccRCC).
Methods
Genes were screened for their mRNA expression from 529 patients in a publicly available ccRCC cohort (TCGA). A cohort of 101 patients with ccRCC served as validation by qRT-PCR mRNA tissue expression analysis.
Results
Expression: B-MYB expression was significantly higher in high-grade tumours (p < 0.0001 and p = 0.048) and in advanced stages (p = 0.005 and p = 0.037) in both cohorts.
Correlation: p53-B-MYB as well as MDM2-B-MYB showed significant correlations in local and low-grade ccRCCs, but not in high grade tumours or advanced stages (r < 0.3 and/or p > 0.05).
Survival: Multivariable Cox regression of the TCGA cohort revealed B-MYB upregulation and low MDM2 expression as predictors for an impaired overall survival (OS) (HR 1.97; p = 0.0003; HR 2.94, p < 0.0001) and progression-free survival (PFS) (HR 2.86; p = 0.0005; HR 1.58, p = 0.046). In the validation cohort, the results were confirmed for OS by univariable, but not multivariable regression: high B-MYB expression (HR = 3.05, p = 0.035) and low MDM2 expression (HR 3.81, p value 0.036).
Conclusion
In ccRCC patients with high-grade tumours and advanced stages, high B-MYB expression is common and is associated with poorer OS and PFS. These patients show a loss of their physiological B-MYB–p53 network correlation, suggesting an additional, alternative regulatory, oncogenic mechanism. Assuming further characterization of its signalling pathways, B-MYB could be a potential therapy target for ccRCC.