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Br J Cancer ; 119(8): 961-970, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30327565

RESUMO

BACKGROUND: CD24 is a cornerstone of tumour progression in urothelial carcinoma of the bladder (UCB). However, its contribution to cancer stem cell (CSC)-like traits and the clinical utility of CD24 as a urinary biomarker for cancer detection have not been determined. METHODS: The functional relevance of CD24 was evaluated using in vitro and in vivo approaches. The clinical utility of CSC-related molecules was assessed in urine samples by quantitative RT-PCR. RESULTS: The knockdown of CD24 attenuated cancer stemness properties. The high-CD24-expressing cells, isolated from patient-derived UCB xenograft tumours, exhibited their enhanced stemness properties. CD24 was overexpressed not only in primary tumours but also in urine from UCB subjects. By assessment of 15 candidate CSC-related molecules in urine samples of a training cohort, a panel of three molecules (CD24, CD49f, and NANOG) was selected. The combination of these three molecules yielded a sensitivity and specificity of 81.7% and 74.3%, respectively, in an independent cohort. A combined set of 84 cases and 207 controls provided a sensitivity and specificity of 82% and 76%, respectively. CONCLUSION: CD24 has a crucial role in maintaining the urothelial cancer stem-like traits and a panel of CSC-related molecules has potential as a urinary biomarker for non-invasive UCB detection.


Assuntos
Biomarcadores Tumorais/urina , Antígeno CD24/metabolismo , Antígeno CD24/urina , Integrina alfa6/urina , Proteína Homeobox Nanog/urina , Células-Tronco Neoplásicas/patologia , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/urina , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígeno CD24/genética , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Pessoa de Meia-Idade , Transplante de Neoplasias , Interferência de RNA , RNA Interferente Pequeno/genética , Esferoides Celulares , Transplante Heterólogo , Células Tumorais Cultivadas , Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/patologia , Urotélio/patologia , Adulto Jovem
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