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Functional and molecular characterization of cancer stem-like cells in bladder cancer
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Orientador(es)
Resumo(s)
Striking evidence associates cancer stem cells (CSCs) to the high recurrence rates and poor survival of patients with muscle-invasive bladder cancer (BC). However, the prognostic implication of those cells in risk stratification is not firmly established, mainly due to the functional and phenotypic heterogeneity of CSCs populations, as well as, to the conflicting data regarding their identification based on a single specific marker. This emphasizes the need to exploit putative CSC-related molecular markers with potential prognostic significance in BC patients. This study aimed to isolate and characterize bladder CSCs making use of different functional and molecular approaches. The data obtained provide strong evidence that muscle-invasive BC is enriched with a heterogeneous stem-like population characterized by enhanced chemoresistance and tumor initiating properties, able to recapitulate the heterogeneity of the original tumor. Additionally, a logistic regression analysis identified a 2-gene stem-like signature (SOX2 and ALDH2) that allows a 93% accurate discrimination between non-muscle-invasive and invasive tumors. Our findings suggest that a stemness-related gene signature, combined with a cluster of markers to more narrowly refine the CSC phenotype, could better identify BC patients that would benefit from a more aggressive therapeutic intervention targeting CSCs population.
Descrição
Funding: This work was supported by the Astellas European Foundation Uro-Oncology Grant 2014; JABA RECORDATI Urology 2011 - Portuguese Society of Urology; Portuguese Foundation for Science and Technology (Strategic Project: PEst-C/SAU/UI3282/2013 and UID/NEU/04539/2013); GAI/FMUC and Santander Totta (Ref. FreitasGomes04.01.13) and Center of Investigation in Environment, Genetics and Oncobiology (CIMAGO), Portugal (Ref. 14/12). Margarida FerreiraTeixeira benefits from a PhD scholarship from the Portuguese Foundation for Science and Technology (Reference SFRH/BD/77314/2011).
Palavras-chave
ALDH Bladder cancer Cancer stem cells Chemoresistance Stemness markers Oncology SDG 3 - Good Health and Well-being