The prognostic value and therapeutic target role of stathmin-1 in urinary bladder cancer
Menée à partir de l'analyse immunohistochimique de tissus tumoraux prélevés sur trois cohortes incluant au total 342 patients atteints d'un cancer de la vessie, puis menée à l'aide d'une lignée cellulaire, cette étude évalue, d'une part, l'association entre l'expression de l'oncoprotéine 18 (stathmine 1) et la survie des patients, puis, d'autre part, l'intérêt d'utiliser cette oncoprotéine comme cible thérapeutique
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.
British Journal of Cancer , résumé, 2013