Biology of Human Tumors ExpressionofAndrogenandEstrogenSignalingComponents and Stem Cell Markers to Predict Cancer Progression and Cancer-SpecificSurvival in PatientswithMetastatic Prostate Cancer

Purpose: Genes of androgen and estrogen signaling cells and stem cell–like cells play crucial roles in prostate cancer. This study aimed topredict clinical failure by identifying these prostate cancer-related genes. Experimental Design: 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-na€ ve prostate cancer with bonemetastasis. Cancerous and stromal tissues were separately collected by laser-capturedmicrodissection. We analyzed the association between clinical failure andmRNA expression of the following genes androgen receptor (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 the curve (AUC) of 1.0 in both sets for Sox2,Her2, andCRP expression in cancer cells, AR and ERa expression in stromal 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; 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 groupswere 90%,32%, and12%in the training set and75%,48%, and0%in the validation set, respectively. Conclusions: Expression levels of androgenand estrogen signaling components and stem cell markers are powerful prognostic tools. Clin Cancer Res; 20(17); 4625–35. 2014 AACR.