The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer

stathmin-1在膀胱癌中的预后价值及治疗靶点作用

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作者:T Hemdan, M Lindén, S B Lind, A V Namuduri, E Sjöstedt, T D de Ståhl, A Asplund, P-U Malmström, U Segersten

Background

The oncoprotein-18/stathmin 1 (STMN1), involved in cell progression and migration, is associated with clinical outcome in breast cancer. Here we

Conclusions

STMN1 protein expression has prognostic significance but is primarily a potential treatment target in urinary bladder cancer.

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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