CD24 regulates cancer stem cell (CSC)-like traits and a panel of CSC-related molecules serves as a non-invasive urinary biomarker for the detection of bladder cancer

• Published in: British journal of cancer Vol. 119; no. 8; pp. 961 - 970
• Main Authors: Ooki, Akira, VandenBussche, Christopher J., Kates, Max, Hahn, Noah M., Matoso, Andres, McConkey, David J., Bivalacqua, Trinity J., Hoque, Mohammad Obaidul
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 16.10.2018; Nature Publishing Group
• Subjects: 631/67/1857; 631/67/589/1336; 631/67/71; Adult; Aged; Aged, 80 and over; Animals; Biomarkers; Biomarkers, Tumor - urine; Biomedical and Life Sciences; Biomedicine; Bladder cancer; Cancer Research; CD24 Antigen - genetics; CD24 Antigen - metabolism; CD24 Antigen - urine; Drug Resistance; Epidemiology; Female; Humans; Integrin alpha6 - urine; Male; Mice; Mice, Inbred NOD; Mice, Knockout; Mice, SCID; Middle Aged; Molecular Medicine; Nanog Homeobox Protein - urine; Neoplasm Transplantation; Neoplastic Stem Cells - pathology; Oncology; Polymerase chain reaction; RNA Interference; RNA, Small Interfering - genetics; Spheroids, Cellular; Stem cells; Transplantation, Heterologous; Tumor Cells, Cultured; Tumors; Urinary Bladder - pathology; Urinary Bladder Neoplasms - diagnosis; Urinary Bladder Neoplasms - pathology; Urinary Bladder Neoplasms - urine; Urine; Urothelial cancer; Urothelial carcinoma; Urothelium - pathology; Xenografts; Young Adult
• ISSN: 0007-0920; 1532-1827; 1532-1827
• DOI: 10.1038/s41416-018-0291-7

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.