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- Title
p63 Expression Defines a Lethal Subset of Muscle-Invasive Bladder Cancers.
- Authors
Woonyoung Choi; Shah, Jay B.; Mai Tran; Svatek, Robert; Marquis, Lauren; I-Ling Lee; Dasom Yu; Adam, Liana; Sijin Wen; Yu Shen; Dinney, Colin; McConkey, David J.; Siefker-Radtke, Arlene
- 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 Ecadherin 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.
- Subjects
STEM cells; BLADDER cancer; MESENCHYMAL stem cells; CADHERINS; VIMENTIN; BIOMARKERS
- Publication
PLoS ONE, 2012, Vol 7, Issue 1, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0030206