Abstract
Purpose
Bladder cancer represents a major cause of malignancy-related morbidity and the most expensive per-patient-to-treat cancer, due to the lifelong surveillance of the patients. Accurate disease prognosis is essential in establishing personalized treatment decisions; yet optimum tools for precise risk stratification remain a competing task. In the present study, we have performed the complete evaluation of TP63 clinical significance in improving disease prognosis.
Methods
The levels of ΔNp63 and TAp63 transcripts of TP63 were quantified in 342 bladder tissue specimens of our screening cohort (n = 182). Hedegaard et al. (Cancer Cell 30:27–42. doi:10.1016/j.ccell.2016.05.004, 2016) (n = 476) and TCGA provisional (n = 413) were used as validation cohorts for NMIBC and MIBC, respectively. Survival analysis was performed using recurrence and progression for NMIBC or mortality for MIBC as endpoint events. Bootstrap analysis was performed for internal validation, while decision curve analysis was used for the evaluation of the clinical net benefit on disease prognosis.
Results
ΔNp63 was significantly expressed in bladder tissues, and was found to be over-expressed in bladder tumors. Interestingly, reduced ΔNp63 levels were correlated with muscle-invasive disease, high-grade tumors and high-EORTC-risk NMIBC patients. Moreover, ΔNp63 loss was independently associated with higher risk for NMIBC relapse (HR = 2.730; p = 0.007) and progression (HR = 7.757; p = 0.016). Hedegaard et al. and TCGA validation cohorts confirmed our findings. Finally, multivariate models combining ΔΝp63 loss with established prognostic markers led to a superior clinical benefit for NMIBC prognosis and risk stratification.
Conclusions
ΔΝp63 loss is associated with adverse outcome of NMIBC resulting in superior prediction of NMIBC early relapse and progression.
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Conception and design: MA and AS, Development of methodology: MAP and MA, Acquisition of data: MAP, MA, PKL, and TT, Analysis and interpretation of data: MA and MAP, Acquired and managed patients: PKL, TT, and KS, Drafting of the manuscript: MAP and MA, Critical revision of the manuscript: AS and KS, Administrative, technical, or material support: AS and KS, Study supervision: AS, Approval of the submitted and final version: all authors.
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Papadimitriou, MA., Avgeris, M., Levis, P.K. et al. ΔNp63 transcript loss in bladder cancer constitutes an independent molecular predictor of TaT1 patients post-treatment relapse and progression. J Cancer Res Clin Oncol 145, 3075–3087 (2019). https://doi.org/10.1007/s00432-019-03028-5
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DOI: https://doi.org/10.1007/s00432-019-03028-5