Novel Biomarkers for Lymph Node Metastasis and Prognosis of Bladder Cancer by Bioinformatics Analysis

Lymph node (LN) metastasis is related to poor prognosis in bladder cancer (BLCA). To explore novel signature genes associated with LN metastasis in BLCA, we identified 17 signature genes with nonzero coefficients to construct the prognostic model, which demonstrated a prognostic accuracy with an area under the curve of 0.706 at 1 year, 0.701 at 3 years, and 0.688 at 5 years. EPN2, CYP4F12, and especially FKBP10, three of the above signature genes, exhibited significant upregulation in BLCA with LN metastasis, thereby contributing to the unfavorable survival of BLCA patients. Meanwhile, we validated that FKBP10 exerts a biological function in bladder cancer metastasis through cytological experiments. Moreover, by utilizing the CIBERSORT algorithm and immunofluorescence assay, we identified and validated a significant upregulation of M0 macrophages, alongside a downregulation of activated NK cells and CD8⁺ T cells, which were associated with the presence of LN metastasis in BLCA. Conclusively, these results will provide new insights for future improvements in diagnosis, treatment, and prognosis evaluation for BLCA patients with LN metastasis.