title: The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer.
abstract: BACKGROUND
  The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we aim to investigate its clinical significance in urinary bladder cancer and its possibilities as a therapeutic target.
  
  
  METHODS
  Immunohistochemical analyses of STMN1 protein expression were performed in three patient cohorts: cohort I (n=115 Ta, n=115 T1, n=112 T2-4 stages), cohort II, based on randomised controlled trials (n=239 T1-T4), and cohort III of primary tumour/matched metastasis (n=90 T1-T4). The effects of STMN1 on cell proliferation and migration were evaluated in the urinary bladder cancer cell line, T24, by inhibiting STMN1-cellular expression using siRNA.
  
  
  RESULTS
  In cohort I, high STMN1 expression correlated to shorter disease-specific survival hazard ratio (HR)=2.04 (95% confidence interval (CI) 1.13-3.68; P=0.02), elevated p53- (P<0.001) and Ki67-protein levels (P<0.001). The survival result was validated in cohort II: HR=1.76 (95% CI 1.04-2.99; P=0.03). In the metastatic bladder cancer material, 70% of the patients were STMN1-positive in both the primary tumour and matched metastases. In vitro, the growth and migration of the T24 cells were significantly reduced (P<0.01, P<0.0001, respectively), when transfecting the cells with STMN1-siRNA.
  
  
  CONCLUSIONS
  STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.
authors: Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
authors: T
authors: T
authors: Hemdan
authors: Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
authors: M
authors: M
authors: Lindén
authors: 1] Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 85, Sweden [2] Department of Chemistry-BMC, Science for Life Laboratory, Uppsala University, Uppsala 751 24, Sweden.
authors: S B
authors: SB
authors: Lind
authors: Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
authors: A V
authors: AV
authors: Namuduri
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 85, Sweden.
authors: E
authors: E
authors: Sjöstedt
authors: Department of Oncology-Pathology, Karolinska Institute, Stockholm 171 76, Sweden.
authors: T D
authors: TD
authors: de Ståhl
authors: Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala 751 85, Sweden.
authors: A
authors: A
authors: Asplund
authors: Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
authors: P-U
authors: PU
authors: Malmström
authors: Department of Surgical Sciences, Uppsala University, Uppsala 751 85, Sweden.
authors: U
authors: U
authors: Segersten
mesh_terms: D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000378:metabolism* / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D005260:Female; D020868:Gene Silencing; D006801:Humans; D053208:Kaplan-Meier Estimate; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011379:Prognosis; D050777:Stathmin / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D019394:Ki-67 Antigen; C493995:STMN1 protein, human; D050777:Stathmin; D016159:Tumor Suppressor Protein p53