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oai:repisalud.isciii.es:20.500.12105/252292024-10-23T09:25:34Zcom_20.500.12105_15322com_20.500.12105_2051col_20.500.12105_16958

00925njm 22002777a 4500 dc Hontecillas-Prieto, Lourdes author Garcia-Dominguez, Daniel J author Vaca, Diego Pascual author Garcia-Mejias, Rosa author Marcilla, David author Ramirez-Villar, Gema L author Saez, Carmen author de Álava, Enrique author 2017 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. http://hdl.handle.net/10668/10746 https://hdl.handle.net/20.500.12105/25229 28061436 10.18632/oncotarget.14491 1949-2553 Oncotarget MDR3 MRP1 Wilms tumours Blastemal stratification Multidrug resistance transporters Multidrug resistance transporter profile reveals MDR3 as a marker for stratification of blastemal Wilms tumour patients.