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

• Published in: Clinical cancer research 2014-09, Vol.20 (17), p.4625-4635
• Main Authors: FUJIMURA, Tetsuya, TAKAHASHI, Satou, INOUE, Satoshi, HOMMA, Yukio, URANO, Tomohiko, TAKAYAMA, Kenichi, SUGIHARA, Toru, OBINATA, Daisuke, YAMADA, Yuta, KUMAGAI, Jimpei, KUME, Haruki, OUCHI, Yasuyoshi
• Format: Article
• Language: English
• Subjects: Aged; Aged, 80 and over; Androgens - genetics; Androgens - metabolism; Antineoplastic agents; Biological and medical sciences; Biomarkers, Tumor; Bone Neoplasms - genetics; Bone Neoplasms - pathology; Bone Neoplasms - secondary; Disease-Free Survival; Estrogens - genetics; Estrogens - metabolism; Gene Expression Regulation, Neoplastic; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Neoplasm Grading; Neoplastic Stem Cells; Nephrology. Urinary tract diseases; Pharmacology. Drug treatments; Prognosis; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - genetics; Prostatic Neoplasms - pathology; Receptors, Androgen - biosynthesis; Receptors, Estrogen - biosynthesis; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-13-1105

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. 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 (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. 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, and CRP expression in cancer cells, AR and ERα 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 ERα 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. Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools.