Nuclear Localization of Robo is Associated with Better Survival in Bladder Cancer

Pathology oncology research: POR

article

Krafft, Ulrich¹  Szarvas, Tibor¹  Reis, Henning³  Ingenwerth, Marc³  Kovalszky, Ilona⁴  Becker, Markus¹  Niedworok, Christian¹  Darr, Christopher¹  Nyirády, Péter²  Hadaschik, Boris¹ 

[1] Department of Urology, Faculty of Medicine, University Duisburg-Essen;Department of Urology, Semmelweis University;Institute of Pathology, Faculty of Medicine, University Duisburg-Essen;1st Institute of Pathology and Experimental Cancer Research, Semmelweis University

关键词: Bladder Cancer;    Robo1;    Robo4;    Nuclear translocation;    Slit2;    Prognosis;    Angiogenesis;   

DOI  :  10.1007/s12253-018-0447-z

来源: Springer

【 摘 要 】

The Slit-Robo pathway has shown to be altered in several malignant diseases. However, its role in bladder cancer is poorly understood. Therefore, we aimed to assess the tissue expression of Robo1 and Robo4 as well as their ligand Slit2 in different stages of bladder cancer to explore possible changes of Slit-Robo signalling during the progression of bladder cancer. Robo1, Robo4 and Slit2 gene expressions were analyzed in 92 frozen bladder cancer tissue samples by using reverse transcription quantitative real-time PCR. Immunohistochemical analyses were performed on 149 formalin-fixed and paraffin-embedded bladder cancer tissue samples. Results were correlated with the clinical and follow-up data by performing both univariable and multivariable analyses. Robo1 and Robo4 nuclear staining intensitiy was significantly higher in low stage and low grade bladder cancer. Elevated Robo1 nuclear staining was associated with better disease-specific survival (DSS) (p = 0.045). Similarly, stronger Robo4 nuclear staining tended to be associated with longer DSS (p = 0.061). We found higher Robo1 and Slit2 gene expression levels in advanced stages of bladder cancer (p = 0.007 and p < 0.001). High Slit2 gene expression was correlated with significantly shorter DSS (p < 0.005), while Robo1 and Robo4 gene expressions were not associated with patients’ prognosis. Our results demonstrate that the nuclear expression of Robo1 and Robo4 is associated with a favourable prognosis suggesting that its translocation into the nucleus represent a posttranslational regulation process which may exhibit an antitumor effect in bladder cancer.

【 授权许可】

Unknown