Predictive value of epithelial-mesenchymal-transition (EMT) signature and PARP-1 in prostate cancer radioresistance

Timothy W. Stark, Patrick J. Hensley, Amanda Spear, Hong Pu, Stephen S. Strup, Natasha Kyprianou

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Introduction: Epithelial-mesenchymal-transition (EMT) has been previously identified as a contributor to prostate cancer progression to metastasis and therapeutic resistance to antiandrogens and radiotherapy. In this study we conducted a retrospective analysis to investigate the significance of radiation-induced EMT and consequential changes to the tumor microenvironment in biochemical recurrence and response to radiotherapy in prostate cancer patients. Methods: Expression profiling and localization for EMT effectors, E-Cadherin, N-Cadherin, β-catenin and Vimentin was assessed in human prostate tumor specimens pre- and post-radiotherapy and correlated with biochemical recurrence. In addition, immunoreactivity of the DNA repair enzyme, polymerase (PARP-1) and the cytoskeletal-remodeling regulator, cofilin was evaluated in prostate tumor specimens pre- and post-radiotherapy and correlated with pre-treatment prostate-specific antigen levels (PSA). Results: Our findings identified that characteristic changes associated with the EMT phenotype and its reversal to mesenchymal-epithelial-transition (MET) within the tumor microenvironment correlate with biochemical recurrence and resistance to radiotherapy among prostate cancer patients. Moreover, elevated PARP-1 expression among the tumor cells undergoing EMT implicates that DNA repair mechanisms may potentially reverse the cytotoxic effects of radiotherapy-induced DNA breaks. Conclusions: Our results suggest that EMT programming effectors, integrated with the actin cytoskeleton regulator cofilin and mesenchymal PARP-1 expression profile provide a signature of potential predictive significance of therapeutic response to radiotherapy in a subset of prostate cancer patients.

Original languageEnglish
Pages (from-to)1583-1591
Number of pages9
JournalProstate
Volume77
Issue number16
DOIs
Publication statusPublished - Dec 1 2017

Keywords

  • PARP-1
  • cofilin
  • prostate tumor recurrence
  • radiotherapy

ASJC Scopus subject areas

  • Oncology
  • Urology

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