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Predictive value of epithelial‐mesenchymal‐transition (EMT) signature and PARP‐1 in prostate cancer radioresistance
Author(s) -
Stark Timothy W.,
Hensley Patrick J.,
Spear Amanda,
Pu Hong,
Strup Stephen S.,
Kyprianou Natasha
Publication year - 2017
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.23435
Subject(s) - prostate cancer , epithelial–mesenchymal transition , radioresistance , cancer research , metastasis , vimentin , medicine , radiation therapy , biochemical recurrence , prostate , oncology , cancer , pathology , biology , prostatectomy , immunohistochemistry
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.