Introduction: To investigate the diagnostic and prognostic value of commonly used immunohistochemical markers regarding high-grade disease, muscle-invasion bladder cancer (MIBC) and survival in bladder cancer. Methods: A total of 477 patients diagnosed with bladder cancer at Peking University Cancer Hospital between 2009 and 2024 were included. The immunohistochemical markers included CK7, CK20, GATA3, Uroplakin 3, CK5/6, P40, P63, Syn, CD56, CGA, Vimentin, S100, LCA, Ki67, P53, Her2, EGFR, PD-L1, PD-1 tumor, PD-1 stroma, and Pan-TRK. Logistic analyses were used to determine the diagnostic value of the markers for high-grade disease and MIBC. Cox regression analyses were used to determine the prognostic value of the markers for survival. Results: We found Ki67 positivity (p < 0.001) and Her2 positivity (p = 0.001) might have an association with high-grade disease, while no marker demonstrated diagnostic value for MIBC. Patients with CK7 positivity (p = 0.012), Uroplakin 3 positivity (p = 0.004), and PD-1 (stroma) positivity (p = 0.037) had better overall survival (OS) than those with negative expression, while Cox regression analyses showed only CK7 positivity (p = 0.025) and Uroplakin 3 positivity (p = 0.008) had prognostic value for better OS. However, considering there were only 2 CK7-negative patients, the sample size might be insufficient to demonstrate its prognostic value. Conclusions: These results suggest that Ki67 positivity and Her2 positivity might have association with high-grade disease, and Uroplakin 3 positivity might have prognostic value for better OS. However, these conclusions require further clarification through larger-scale studies in the future.

Disitamab Vedotin has shown good therapeutic efficacy against bladder cancer. Although its mechanism is clear, the regulation of gene expression in bladder cancer cells by Disitamab Vedotin is not fully understood. We searched the GEO database and identified the GSE237789 dataset, in which researchers treated the bladder cancer cell line SW780 with Disitamab Vedotin and performed high-throughput transcriptome sequencing. Compared with the control SW780 cells, the expression levels of the vast majority of genes (16,223/16,390, 98.98%) in Disitamab Vedotin-treated SW780 cells remained unchanged. Only one hundred fifty-nine genes (0.97%) were upregulated, and eight genes (0.05%) were downregulated. Enrichment analysis results showed that the related differentially expressed genes (DEGs) were mainly enriched in the TNF signaling pathway, NF-κB signaling pathway, and other pathways. Protein–protein interaction analysis revealed that 10 genes, TNF, IL1B, IL1A, CXCL8, CXCL1, CCL2, MMP9, ICAM1, CXCL10, and CCL20, had the highest connectivity, and all of these genes belong to the TNF signaling pathway. These results suggest that the TNF signaling pathway is the key pathway regulated by Disitamab Vedotin in bladder cancer cells, which may represent a stress response of bladder cancer cells to Disitamab Vedotin.