Crosstalk between ZEB1 expression and CD163+ Tumor-Associated Macrophages in Muscle-Invasive Urothelial Carcinoma

OBJECTIVE: There is an urgent need to investigate the molecular mechanisms underlying the invasion and metastasis of bladder cancer to develop more effective therapeutic strategies and thereby reduce tumor-related morbidity and mortality. This study aimed to evaluate the prognostic significance of ZEB1 expression in bladder carcinoma (BC) and its association with tumor-associated macrophages (TAMs) within the tumor microenvironment (TME). METHODS: A retrospective analysis was conducted on 48 patients with muscle-invasive bladder carcinoma (MIBC) who underwent radical cystectomy. Immunohistochemical staining for ZEB1 and CD163 was performed, followed by statistical analysis to assess their association with various clinicopathological parameters, including survival outcomes. RESULTS: High ZEB1 expression was significantly correlated with lymphovascular invasion, tumor necrosis, advanced disease stage, and nodal metastasis. Furthermore, elevated ZEB1 expression was associated with significantly worse 3-year overall survival (OS) and disease-free survival (DFS). Similarly, a high density of CD163+TAMs within TME was associated with adverse clinicopathological parameters and poor survival outcomes. Notably, a strong positive correlation was observed between ZEB1 expression and the density of CD163+ TAMs within the TME of BC. Multivariate analysis identified ZEB1 expression as an independent predictor of recurrence and nodal metastasis. CONCLUSION: Elevated ZEB1 expression is strongly associated with poor prognosis in BC and closely correlated with an increased density of CD163+TAMs, further contributing to adverse outcomes. These findings highlight the potential of ZEB1 as a prognostic biomarker and underscore the therapeutic relevance of targeting TAMs in the management of BC.