title: Association of tumour microRNA profiling with outcomes in patients with advanced urothelial carcinoma receiving first-line platinum-based chemotherapy.
abstract: Tumour expression of selected microRNAs (miRs) correlates with cisplatin efficacy in multiple cancers. We investigated the role of selected miRs in patients receiving cisplatin-based therapy for advanced urothelial carcinoma (UC).
  
  
  
  RNA was extracted from formalin-fixed paraffin-embedded tumour from 83 advanced UC patients who received cisplatin. A miR panel based on relevance for platinum sensitivity and UC was studied by quantitative reverse transcription quantitative PCR (RT-qPCR). Association of progression-free survival (PFS) with miR expression was analysed using cox regression. Selected TFs were chosen by association with the panel of miRs using the Transcription Regulation algorithm (GeneGo MetaCore+MetaDrug version 6.23 build 67496). Bladder cancer (BC) cell lines were used to investigate the previously described role of miR-21 mediating cisplatin sensitivity.
  
  
  
  The 83 patients had a median PFS of 8 months. In multivariate analysis, higher levels of E2F1 (P=0.01, HR: 1.95 (1.14, 3.33)), miR-21 (P=0.01, HR: 2.01 (1.17, 3.45)) and miR-372 (P=0.05, HR: 1.70 (1.00, 2.89)) were associated with a shorter PFS. In the 8 BC cell lines, miR-21 was not shown to be necessary nor sufficient for modulating cisplatin sensitivity.
  
  
  
  In metastatic UC patients treated with cisplatin-based therapy, high primary tumour levels of E2F1, miR-21 and miR-372 are associated with poor PFS independent of clinical prognostic factors. The in vitro study could not confirm miR-21 levels role in modulating platinum sensitivity.
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.|Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.|Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Joaquim
authors.initials: J
authors.lastname: Bellmunt
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Chensheng Willa
authors.initials: CW
authors.lastname: Zhou
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Mullane
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Lillian
authors.initials: L
authors.lastname: Werner
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.|Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Mary-Ellen
authors.initials: ME
authors.lastname: Taplin
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: André P
authors.initials: AP
authors.lastname: Fay
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.|Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.|Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: Toni K
authors.initials: TK
authors.lastname: Choueiri
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Anna
authors.initials: A
authors.lastname: Orsola
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.|Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.|Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.
authors.forename: David Y
authors.initials: DY
authors.lastname: Takeda
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.|Departement of Medical Oncology, Brigham and Women's Cancer Center, Brigham and Women's Cancer Center, Boston, MA 02115, USA.|Departement of Medical Oncology, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA.|The Eli and Edythe L. Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: William C
authors.initials: WC
authors.lastname: Hahn
authors.affiliation: The Eli and Edythe L. Broad Institute, 415 Main Street, Cambridge, MA 02142, USA.
authors.forename: Jaegil
authors.initials: J
authors.lastname: Kim
authors.affiliation: Departement of Medical Oncology, University of Alabama at Birmingham (UAB), 1720 2nd Avenue S, Birmingham, AL 35233, USA.
authors.forename: Guru
authors.initials: G
authors.lastname: Sonpavde
authors.affiliation: Departement of Medical Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215, USA.
authors.forename: Michaela
authors.initials: M
authors.lastname: Bowden
mesh_terms: D002277:Carcinoma / Q000188:drug therapy* / Q000235:genetics*; D002460:Cell Line; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D057809:HEK293 Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009944:Organoplatinum Compounds / Q000627:therapeutic use*; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000235:genetics; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000235:genetics*
chemical_list: D035683:MicroRNAs; D009944:Organoplatinum Compounds; D002945:Cisplatin