Impact of myeloid cell signature on the overall survival of patients with bladder cancer

Bladder cancer (BLC) is one of the most prevalent tumors in the urinary system, posing a significant public health threat. Myeloid cells play a crucial role in the tumor microenvironment, contributing to tumor progression and treatment response. Our objective is to develop prognostic models based on myeloid cell markers to predict the prognosis of BLC and investigate the underlying mechanisms. The prognostic relevance of each myeloid marker was evaluated through immunohistochemistry and survival analysis. The prognostic model was constructed using LASSO regression analysis. Multiple fluorescence immunohistochemical staining and RNA sequencing were employed to investigate the potential mechanisms underlying prognosis differences in different risk groups. We observed that CD68 expression in the tumor region correlated with a favorable prognosis in patients with BLC, while CD14, CD74, CD163, and S100A12 were associated with an poor prognosis in these patients. Subsequently, we developed a myeloid risk score (MRS), which was validated across various cohorts and demonstrated excellent predictive capability. We observed a significant upregulation of the PI3K-AKT signaling pathway in the MRS-high group. Moreover, there was an increased expression of PD-L1, FOXP3, and CD11b accompanied by a decreased CD8+ T cell infiltration in the tumor microenvironment of the MRS-high group, indicating pronounced immunosuppression. Finally, potential targets and therapeutic agents for the MRS-high group were predicted. These findings provide a robust risk prediction model for BLC patients that can facilitate personalized treatment.