Expression of Androgen and Estrogen Signaling Components and Stem Cell Markers to Predict Cancer Progression and Cancer-Specific Survival in Patients with Metastatic Prostate Cancer

Purpose: Genes of androgen and estrogen signaling cells and stem cell–like cells play crucial roles inprostate cancer. This study aimed to predict clinical failure by identifying these prostate cancer-related genes.Experimental Design: We developed models to predict clinical failure using biopsy samples from atraining set of 46 and an independent validation set of 30 patients with treatment-na€?ve prostate cancer withbone metastasis. Cancerous and stromal tissues were separately collected by laser-captured microdissection.We analyzed the association between clinical failure andmRNAexpression of the following genes androgenreceptor (AR) and its related genes (APP, FOX family, TRIM 36, Oct1, and ACSL 3), stem cell–like molecules(Klf4, c-Myc, Oct 3/4, and Sox2), estrogen receptor (ER), Her2, PSA, and CRP. Results: Logistic analyses to predict prostate-specific antigen (PSA) recurrence showed an area under thecurve (AUC) of 1.0 in both sets for Sox2, Her2, and CRP expression in cancer cells, AR and ERa expression instromal cells, and clinical parameters. We identified 10 prognostic factors for cancer-specific survival (CSS):Oct1, TRIM36, Sox2, and c-Myc expression in cancer cells; AR, Klf4, and ERa expression in stromal cells; andPSA, Gleason score, and extent of disease.Onthe 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 3groups were 90%, 32%, and12%in the training set and 75%, 48%, and0%in the validation set, respectively. Conclusions: Expression levels of androgen- and estrogen signaling components and stem cell markersare powerful prognostic tools.