Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients.
Oncotarget
; 8(7): 11173-11186, 2017 Feb 14.
Article
em En
| MEDLINE
| ID: mdl-28061436
ABSTRACT
Wilms tumour (WT) is the most common renal tumour in children. Most WT patients respond to chemotherapy, but subsets of tumours develop resistance to chemotherapeutic agents, which is a major obstacle in their successful treatment. Multidrug resistance transporters play a crucial role in the development of resistance in cancer due to the efflux of anticancer agents out of cells. The aim of this study was to explore several human multidrug resistance transporters in 46 WT and 40 non-neoplastic control tissues (normal kidney) from patients selected after chemotherapy treatment SIOP 93-01, SIOP 2001. Our data showed that the majority of the studied multidrug resistance transporters were downregulated or unchanged between tumours and control tissues. However, BCRP1, MDR3 and MRP1 were upregulated in tumours versus control tissues. MDR3 and MRP1 overexpression correlated with high-risk tumours (SIOP classification) (p = 0.0022 and p < 0.0001, respectively) and the time of disease-free survival was significantly shorter in patients with high transcript levels of MDR3 (p = 0.0359). MDR3 and MRP1 play a role in drug resistance in WT treatment, probably by alteration of an unspecific drug excretion system. Besides, within the blastemal subtype, we observed patients with low MDR3 expression were significantly associated with a better outcome than patients with high MDR3 expression. We could define two types of blastemal WT associated with different disease outcomes, enabling the stratification of blastemal WT patients based on the expression levels of the multidrug resistance transporter MDR3.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Biomarcadores Tumorais
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Tumor de Wilms
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Resistência a Múltiplos Medicamentos
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Subfamília B de Transportador de Cassetes de Ligação de ATP
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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:
Child
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Child, preschool
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Humans
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Infant
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article