The Prognostic Value and Therapeutic Target Role of Stathmin-1 in Urinary Bladder Cancer

Overview

Journal Br J Cancer

Specialty Oncology

Date 2014 Jul 30

PMID 25072257

Citations 21

Authors

T Hemdan

M Linden

S B Lind

A V Namuduri

E Sjostedt

T D de Stahl

A Asplund

P-U Malmstrom

U Segersten

Affiliations

Soon will be listed here.

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.

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