B-MYB-p53-related relevant regulator for the progression of clear cell renal cell carcinoma.
J Cancer Res Clin Oncol
; 147(1): 129-138, 2021 Jan.
Article
em En
| MEDLINE
| ID: mdl-32951068
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.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Carcinoma de Células Renais
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Biomarcadores Tumorais
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Regulação Neoplásica da Expressão Gênica
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Transativadores
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Proteína Supressora de Tumor p53
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Proteínas de Ciclo Celular
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Neoplasias Renais
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article