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

Br J Cancer. 2018 Oct;119(8):961-970. doi: 10.1038/s41416-018-0291-7. Epub 2018 Oct 17.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Biomarkers, Tumor / urine*
  • CD24 Antigen / genetics
  • CD24 Antigen / metabolism*
  • CD24 Antigen / urine*
  • Female
  • Humans
  • Integrin alpha6 / urine*
  • Male
  • Mice
  • Mice, Inbred NOD
  • Mice, Knockout
  • Mice, SCID
  • Middle Aged
  • Nanog Homeobox Protein / urine*
  • Neoplasm Transplantation
  • Neoplastic Stem Cells / pathology*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Spheroids, Cellular
  • Transplantation, Heterologous
  • Tumor Cells, Cultured
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / diagnosis*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / urine*
  • Urothelium / pathology
  • Young Adult

Substances

  • Biomarkers, Tumor
  • CD24 Antigen
  • CD24 protein, human
  • Integrin alpha6
  • NANOG protein, human
  • Nanog Homeobox Protein
  • RNA, Small Interfering