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Journal of Cancer Research and Clinical Oncology

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19.09.2020 | Original Article – Cancer Research

B-MYB—p53-related relevant regulator for the progression of clear cell renal cell carcinoma

verfasst von: M. Nientiedt, K. Müller, K. Nitschke, P. Erben, A. Steidler, S. Porubsky, Z. V. Popovic, F. Waldbillig, J. Mühlbauer, M. C. Kriegmair

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 1/2021

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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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Titel: B-MYB—p53-related relevant regulator for the progression of clear cell renal cell carcinoma
verfasst von: M. Nientiedt
K. Müller
K. Nitschke
P. Erben
A. Steidler
S. Porubsky
Z. V. Popovic
F. Waldbillig
J. Mühlbauer
M. C. Kriegmair
Publikationsdatum: 19.09.2020
Verlag: Springer Berlin Heidelberg
Erschienen in: Journal of Cancer Research and Clinical Oncology / Ausgabe 1/2021
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI: https://doi.org/10.1007/s00432-020-03392-7

Springer Medizin

B-MYB—p53-related relevant regulator for the progression of clear cell renal cell carcinoma