Nuclear Expression of Dynamin 2 Is Associated With Tumor Aggressiveness in Bladder Cancer Patients: A Bioinformatics and Experimental Approach

Background: Dynamin 2 (DNM2) is aberrantly expressed in different malignancies and exerts a function in tumor progression.

Aims: This study, for the first time, aimed to evaluate the clinical and prognostic value of DNM2 in the pathophysiology of bladder cancer using bioinformatics analysis and experimental evaluation.

Methods and results: We analyzed gene expression of DNM2 in bladder tumor by GEPIA2 and GENT2 platforms. Cluster subnetworks were recognized from the protein-protein interaction (PPI) network using the MCODE plugin to screen the key genes. Subsequently, the pathway enrichment analysis was evaluated. Then, the immunohistochemical examination was conducted on 209 paraffin-embedded bladder cancer samples to determine the expression pattern and clinical importance of DNM2. Our data mining findings demonstrated dysregulation of DNM2 gene expression in bladder cancer. The results of pathway and PPI network analyses indicated that DNM2 might be involved in the development of bladder cancer by influencing various signaling pathways. Our IHC results represented remarkably higher DNM2 expression in bladder tumor samples compared to normal tissue samples adjacent to tumor. A statistically significant association was identified between DNM2 expression in the nucleus and higher histological grade (p = 0.026), advanced pT stage (p = 0.016), muscular invasion (p = 0.007), tumor recurrence (p = 0.030), and distant metastasis (p < 0.001). Moreover, the nuclear DNM2 expression was observed to have prognostic significance for disease-specific survival (DSS) using a log-rank test (p = 0.028).

Conclusion: These findings suggest that nuclear DNM2 expression could be a putative indicator of bladder tumor progression owing to its association with elevated cancer aggressiveness.