p63 expression defines a lethal subset of muscle-invasive bladder cancers

Woonyoung Choi, Jay B. Shah, Mai Tran, Robert Svatek, Lauren Marquis, I. Ling Lee, Dasom Yu, Liana Adam, Sijin Wen, Yu Shen, Colin Dinney, David J. McConkey, Arlene Siefker-Radtke

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Background: p63 is a member of the p53 family that has been implicated in maintenance of epithelial stem cell compartments. Previous studies demonstrated that p63 is downregulated in muscle-invasive bladder cancers, but the relationship between p63 expression and survival is not clear. Methodology/Principal Findings: We used real-time PCR to characterize p63 expression and several genes implicated in epithelial-to-mesenchymal transition (EMT) in human bladder cancer cell lines (n = 15) and primary tumors (n = 101). We correlated tumor marker expression with stage, disease-specific (DSS), and overall survival (OS). Expression of E-cadherin and p63 correlated directly with one another and inversely with expression of the mesenchymal markers Zeb-1, Zeb-2, and vimentin. Non-muscle-invasive (Ta and T1) bladder cancers uniformly expressed high levels of E-cadherin and p63 and low levels of the mesenchymal markers. Interestingly, a subset of muscle-invasive (T2-T4) tumors maintained high levels of E-cadherin and p63 expression. As expected, there was a strongly significant correlation between EMT marker expression and muscle invasion (p&0.0001). However, OS was shorter in patients with muscle-invasive tumors that retained p63 (p = 0.007). Conclusions/Significance: Our data confirm that molecular markers of EMT are elevated in muscle-invasive bladder cancers, but interestingly, retention of the "epithelial" marker p63 in muscle-invasive tumors is associated with a worse outcome.

Original languageEnglish (US)
Article numbere30206
JournalPloS one
Volume7
Issue number1
DOIs
StatePublished - Jan 10 2012

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)
  • General

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    Choi, W., Shah, J. B., Tran, M., Svatek, R., Marquis, L., Lee, I. L., Yu, D., Adam, L., Wen, S., Shen, Y., Dinney, C., McConkey, D. J., & Siefker-Radtke, A. (2012). p63 expression defines a lethal subset of muscle-invasive bladder cancers. PloS one, 7(1), [e30206]. https://doi.org/10.1371/journal.pone.0030206