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Culture of Bladder Cancer Organoids as Precision Medicine Tools
Published on: December 28, 2021
Nuclear Localization of Robo is Associated with Better Survival in Bladder Cancer
Ulrich Krafft1, Henning Reis2, Marc Ingenwerth2
1Department of Urology, Faculty of Medicine, University Duisburg-Essen, Hufelandstr 55, 45147, Essen, Germany.
Abstract:
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.
Insights
Nuclear expression of Robo1 and Robo4 in bladder cancer correlates with better prognosis. Conversely, higher gene expression of Slit2 and Robo1/Robo4 in advanced stages suggests a role in bladder cancer progression.
Area of Science:
- Oncology
- Molecular Biology
- Cell Signaling
Background:
- The Slit-Robo pathway is implicated in various cancers, but its function in bladder cancer remains unclear.
- Understanding Slit-Robo signaling is crucial for identifying potential therapeutic targets in bladder cancer.
Purpose of the Study:
- To investigate the expression of Robo1, Robo4, and Slit2 in bladder cancer tissues.
- To correlate Slit-Robo pathway component expression with bladder cancer stage, grade, and patient prognosis.
Main Methods:
- Gene expression analysis using reverse transcription quantitative real-time PCR on 92 bladder cancer samples.
- Immunohistochemical analysis of 149 bladder cancer samples to assess protein expression.
- Statistical correlation of expression data with clinical and follow-up data.
Main Results:
- Higher nuclear staining intensity for Robo1 and Robo4 was observed in low-stage and low-grade bladder cancer.
- Elevated nuclear Robo1 staining was linked to better disease-specific survival (DSS).
- Increased gene expression of Robo1 and Slit2 was found in advanced bladder cancer stages, with high Slit2 correlating with shorter DSS.
Conclusions:
- Nuclear expression of Robo1 and Robo4 may indicate a favorable prognosis in bladder cancer.
- The translocation of Robo1 and Robo4 to the nucleus could be a post-translational regulatory mechanism with antitumor effects.
- Slit-Robo pathway dysregulation, particularly increased gene expression in advanced stages, might contribute to bladder cancer progression.
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