title: 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.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  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, 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.
  
  
  CONCLUSIONS
  Expression levels of androgen- and estrogen signaling components and stem cell markers are powerful prognostic tools.
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. fujimurat-uro@h.u-tokyo.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: Department of Urology, Graduate School of Medicine, The Nihon University, Tokyo, Japan.
authors.forename: Satou
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Urano
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Kenichi
authors.initials: K
authors.lastname: Takayama
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Sugihara
authors.affiliation: Department of Urology, Graduate School of Medicine, The Nihon University, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Obinata
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Jimpei
authors.initials: J
authors.lastname: Kumagai
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Haruki
authors.initials: H
authors.lastname: Kume
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasuyoshi
authors.initials: Y
authors.lastname: Ouchi
authors.affiliation: Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan. Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Inoue
authors.affiliation: Department of Urology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Homma
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000728:Androgens / Q000235:genetics* / Q000378:metabolism; D014408:Biomarkers, Tumor; D001859:Bone Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D004967:Estrogens / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D014411:Neoplastic Stem Cells; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D011944:Receptors, Androgen / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000096:biosynthesis*
chemical_list: D000728:Androgens; D014408:Biomarkers, Tumor; D004967:Estrogens; C000715467:KLF4 protein, human; D000090062:Kruppel-Like Factor 4; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D017430:Prostate-Specific Antigen