mRNA-Expression of KRT5 and KRT20 Defines Distinct Prognostic Subgroups of Muscle-Invasive Urothelial Bladder Cancer Correlating with Histological Variants.
Int J Mol Sci
; 19(11)2018 10 30.
Article
em En
| MEDLINE
| ID: mdl-30380731
ABSTRACT
Recently, muscle-invasive bladder cancer (MIBC) has been subclassified by gene expression profiling, with a substantial impact on therapy response and patient outcome. We tested whether these complex molecular subtypes of MIBC can be determined by mRNA detection of keratin 5 (KRT5) and keratin 20 (KRT20). Reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) was applied to quantify gene expression of KRT5 and KRT20 using TaqMan®-based assays in 122 curatively treated MIBC patients (median age 68.0 years). Furthermore, in silico analysis of the MD Anderson Cancer Center (MDACC) cohort (GSE48277 + GSE47993) was performed. High expression of KRT5 and low expression of KRT20 were associated with significantly improved recurrence-free survival (RFS) and disease-specific survival disease specific survival (DSS 5-year DSS for KRT5 high 58%; 5-year DSS for KRT20 high 29%). KRT5 and KRT20 were associated with rates of lymphovascular invasion and lymphonodal metastasis. The combination of KRT5 and KRT20 allowed identification of patients with a very poor prognosis (KRT20âº/KRT5-, 5-year DSS 0%, p < 0.0001). In silico analysis of the independent MDACC cohorts revealed congruent results (5-year DSS for KRT20 low vs. high 84% vs. 40%, p = 0.042). High KRT20-expressing tumors as well as KRT20âº/KRT- tumors were significantly enriched with aggressive urothelial carcinoma variants (micropapillary, plasmacytoid, nested).
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Texto completo:
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Bases de dados:
MEDLINE
Assunto principal:
Neoplasias da Bexiga Urinária
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RNA Mensageiro
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RNA Neoplásico
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Regulação Neoplásica da Expressão Gênica
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Urotélio
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Queratina-5
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Proteínas de Neoplasias
Tipo de estudo:
Prognostic_studies
Limite:
Female
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Humans
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Male
Idioma:
En
Revista:
Int J Mol Sci
Ano de publicação:
2018
Tipo de documento:
Article
País de afiliação:
Alemanha