Abstract
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.
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Data availability
The authors confirm that the data supporting the findings of this study are available within the article and its Online Resource.
Code availability
Not applicable.
Abbreviations
- AJCC:
-
American Joint Committee on Cancer
- ccRCC:
-
Clear cell renal cell carcinoma
- FFPE:
-
Formaldehyde and embedded in paraffin
- HR:
-
Hazard ratio
- IQR:
-
Interquartile range
- OS:
-
Overall survival
- PFS:
-
Progression-free survival
- RCC:
-
Renal cell carcinoma
- STRAP:
-
Serine-threonine kinase receptor-associated protein
- UICC:
-
Union for International Cancer Control
- TCGA:
-
The Cancer Genome Atlas
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Acknowledgements
We would like to thank the entire team of the Urological Research Laboratory at the University Hospital Mannheim, who provided insights and expertise that greatly assisted in the realization of the experiments.
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MN: guarantor of integrity of the entire study, statistical analysis, manuscript preparation; KM: experimental studies/data analysis; KN and AS experimental guidance; ZVP and SP pathological validation; PE, JM, and FW: manuscript editing; MCK: study concepts and design, guarantor of integrity of the entire study, manuscript editing.
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Nientiedt, M., Müller, K., Nitschke, K. et al. B-MYB—p53-related relevant regulator for the progression of clear cell renal cell carcinoma. J Cancer Res Clin Oncol 147, 129–138 (2021). https://doi.org/10.1007/s00432-020-03392-7
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DOI: https://doi.org/10.1007/s00432-020-03392-7