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首页> 美国卫生研究院文献>Oncotarget >Functional and molecular characterization of cancer stem-like cells in bladder cancer: a potential signature for muscle-invasive tumors
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Functional and molecular characterization of cancer stem-like cells in bladder cancer: a potential signature for muscle-invasive tumors

机译：膀胱癌中癌干样细胞的功能和分子表征：肌肉浸润性肿瘤的潜在特征

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摘要

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.
机译：惊人的证据表明，癌症干细胞（CSC）与肌肉浸润性膀胱癌（BC）患者的高复发率和较差的存活率相关。然而，这些细胞在危险分层中的预后意义尚不确定，这主要归因于CSC群体的功能和表型异质性，以及有关基于单个特定标记物进行鉴定的相互矛盾的数据。这项研究强调需要在BC患者中开发具有潜在预后意义的推定CSC相关分子标记。本研究旨在利用不同的功能和分子方法来分离和表征膀胱CSC。获得的数据提供了强有力的证据，表明肌肉侵袭性BC富含异质茎样种群，其特征是增强了化学抗性和肿瘤起始特性，能够概括原始肿瘤的异质性。此外，通过逻辑回归分析确定了2个基因的茎样特征（SOX2和ALDH2），可以准确区分非肌肉侵袭性和侵袭性肿瘤93％。一组标记以更狭窄地完善CSC表型，可以更好地识别BC患者，这些患者将从针对CSC人群的更积极的治疗干预中受益。

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