Abstract

<div>Abstract<p><b>Purpose:</b> Genes of androgen and estrogen signaling cells and stem cell–like cells play crucial roles in prostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes.</p><p><b>Experimental Design:</b> We developed models to predict clinical failure using biopsy samples from a training set of 46 and an independent validation set of 30 patients with treatment-naïve prostate cancer with bone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection. We analyzed the association between clinical failure and mRNA expression of the following genes androgen receptor (<i>AR</i>) and its related genes (<i>APP</i>, <i>FOX</i> family, <i>TRIM 36</i>, <i>Oct1</i>, and <i>ACSL 3</i>), stem cell–like molecules (<i>Klf4</i>, <i>c-Myc</i>, <i>Oct 3/4</i>, and <i>Sox2</i>), estrogen receptor (<i>ER</i>), <i>Her2</i>, <i>PSA</i>, and <i>CRP</i>.</p><p><b>Results:</b> Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under the curve (AUC) of 1.0 in both sets for <i>Sox2</i>, <i>Her2</i>, and <i>CRP</i> expression in cancer cells, <i>AR</i> and <i>ERα</i> expression in stromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS): <i>Oct1</i>, <i>TRIM36</i>, <i>Sox2</i>, and <i>c-Myc</i> expression in cancer cells; <i>AR</i>, <i>Klf4</i>, and <i>ERα</i> expression in stromal cells; and PSA, Gleason score, and extent of disease. On the basis of these factors, patients were divided into favorable-, intermediate-, and poor-risk groups according to the number of factors present. Five-year CSS rates for the 3 groups were 90%, 32%, and 12% in the training set and 75%, 48%, and 0% in the validation set, respectively.</p><p><b>Conclusions:</b> Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools. <i>Clin Cancer Res; 20(17); 4625–35. ©2014 AACR</i>.</p></div>

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