title: Androgen deprivation modulates gene expression profile along prostate cancer progression.
abstract: Androgen deprivation therapy (ADT) is the standard of care for metastatic prostate cancer and initially induces tumor regression, but invariably results in castration-resistant prostate cancer through various mechanisms, incompletely discovered. Our aim was to analyze the dynamic modulation, determined by ADT, of the expression of selected genes involved in the pathogenesis and progression of prostate cancer (TMPRSS2:ERG, WNT11, SPINK1, CHGA, AR, and SPDEF) using real-time polymerase chain reaction in a series of 59 surgical samples of prostate carcinomas, including 37 cases preoperatively treated with ADT and 22 untreated cases, and in 43 corresponding biopsies. The same genes were analyzed in androgen-deprived and control LNCaP cells. Three genes were significantly up-modulated (WNT11 and AR) or down-modulated (SPDEF) in patients treated with ADT versus untreated cases, as well as in androgen-deprived LNCaP cells. The effect of ADT on CHGA gene up-modulation was almost exclusively detected in cases positive for the TMPRSS2:ERG fusion. The correlation between biopsy and surgical samples was poor for most of the tested genes. Gene expression analysis of separate tumor areas from the same patient showed an extremely heterogeneous profile in the 6 tested cases (all untreated). In conclusion, our results strengthened the implication of ADT in promoting a prostate cancer aggressive phenotype and identified potential biomarkers, with special reference to the TMPRSS2:ERG fusion, which might favor the development of neuroendocrine differentiation in hormone-treated patients. However, intratumoral heterogeneity limits the use of gene expression analysis as a potential prognostic or predictive biomarker in patients treated with ADT.
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: marco.volante@unito.it.
authors.forename: Marco
authors.initials: M
authors.lastname: Volante
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: tota.daniele@gmail.com.
authors.forename: Daniele
authors.initials: D
authors.lastname: Tota
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: gio.jessica@gmail.com.
authors.forename: Jessica
authors.initials: J
authors.lastname: Giorcelli
authors.affiliation: Division of Pathology at San Luigi Hospital, Orbassano, Orbassano, Turin 10043, Italy. Electronic address: e.bollito@libero.it.
authors.forename: Enrico
authors.initials: E
authors.lastname: Bollito
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: francesca.napoli2386@gmail.com.
authors.forename: Francesca
authors.initials: F
authors.lastname: Napoli
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: simona.vatrano@unito.it.
authors.forename: Simona
authors.initials: S
authors.lastname: Vatrano
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: consuelo.buttigliero@gmail.com.
authors.forename: Consuelo
authors.initials: C
authors.lastname: Buttigliero
authors.affiliation: Division of Pathology, Città della Salute Hospital, Turin 10126, Italy. Electronic address: luca.molinaro@unito.it.
authors.forename: Luca
authors.initials: L
authors.lastname: Molinaro
authors.affiliation: Division of Urology, Città della Salute Hospital, Turin 10126, Italy. Electronic address: paolo.gontero@unito.it.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gontero
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: francesco.porpiglia@unito.it.
authors.forename: Francesco
authors.initials: F
authors.lastname: Porpiglia
authors.affiliation: Division of Medical Oncology at San Luigi Hospital, Orbassano, Turin 10043, Italy. Electronic address: marcello.tucci@gmail.com.
authors.forename: Marcello
authors.initials: M
authors.lastname: Tucci
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: mauro.papotti@unito.it.
authors.forename: Mauro
authors.initials: M
authors.lastname: Papotti
authors.affiliation: Department of Medical and Surgical Specialties, Radiological Sciences, and Public Health, University of Brescia, Brescia 25121, Italy. Electronic address: alfredo.berruti@gmail.com.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Berruti
authors.affiliation: Department of Oncology at San Luigi Hospital, University of Turin, Orbassano, Turin 10043, Italy. Electronic address: ida.rapa@unito.it.
authors.forename: Ida
authors.initials: I
authors.lastname: Rapa
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D000368:Aged; D000726:Androgen Antagonists / Q000627:therapeutic use*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D001706:Biopsy; D045744:Cell Line, Tumor; D017024:Chemotherapy, Adjuvant; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D015514:Oncogene Proteins, Fusion / Q000235:genetics; D011237:Predictive Value of Tests; D011468:Prostatectomy; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology / Q000601:surgery; D060888:Real-Time Polymerase Chain Reaction; D015203:Reproducibility of Results; D059467:Transcriptome / Q000187:drug effects*; D016896:Treatment Outcome
chemical_list: D000726:Androgen Antagonists; D018931:Antineoplastic Agents, Hormonal; D014408:Biomarkers, Tumor; D015514:Oncogene Proteins, Fusion; C515553:TMPRSS2-ERG fusion protein, human
keywords: Androgen deprivation; Gene expression; Modulation; Neuroendocrine differentiation; Prostate cancer; TMPRSS2:ERG translocation