High SPDEF May Identify Patients Who Will Have a Prolonged Response to Androgen Deprivation Therapy

Overview

Journal Prostate

Date 2013 Dec 31

PMID 24375440

Citations 8

Authors

Andrew C Haller

Wei Tan

Rochelle Payne-Ondracek

Willie Underwood

Lili Tian

Carl Morrison

Fengzhi Li

Affiliations

Soon will be listed here.

Abstract

Background: Due to the indolent nature of prostate cancer, new prognostic measures are needed to identify patients with life threatening disease. SAM pointed domain-containing Ets transcription factor (SPDEF) has been associated with good prognosis and demonstrates an intimate relationship with the androgen receptor (AR), however its role in prostate cancer progression remains unclear.

Methods: A tissue microarray constructed from cores of 713 consecutive radical prostatectomy specimens were immunohistochemically stained for SPDEF and correlated with progression free and metastatic free survival. In vitro studies assessed growth rate, migration, and sensitivity to bicalutamide to explore mechanisms behind the tissue microarray observations.

Results: Patients with high SPDEF demonstrate longer metastases free survival after receiving the standard of care (HR = 9.80, P = 0.006). SPDEF expression corresponded with bicalutamide growth inhibition and apoptosis induction in all cell lines studied. In addition, a feedforward loop of AR-SPEF expression regulation is observed.

Conclusions: SPDEF may be clinically useful to identify patients who will have extended benefits from androgen deprivation therapy. In vitro observations suggest SPDEF mediates initial sensitivity to androgen deprivation therapy through both AR regulation and downstream events.

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