Suppression of LTBP1 enhances the sensitivity of bladder cancer to cisplatin.

Cisplatin-based chemotherapy is the primary treatment for advanced bladder cancer; however, numerous patients experience treatment failure because of chemoresistance. Therefore, it is crucial to identify drivers of chemoresistance and determine strategies to counteract them to improve prognosis in bladder cancer patients. This study performed proteomics analysis of clinical samples of cisplatin-naïve and resistant bladder cancer tissues. Furthermore, the GEO and TCGA datasets were integrated, which revealed latent transforming growth factor β binding protein 1 (LTBP1) as a potential gene associated with chemoresistance in bladder cancer. LTBP1 expression was correlated with clinical stage and patient survival. LTBP1 knockdown in bladder cancer cells inhibited proliferation, migration, invasion, and chemoresistance via TGF-β-mediated epithelial-mesenchymal transition. Subcutaneous tumor and lung metastasis mouse models revealed that LTBP1 inhibition combined with cisplatin treatment significantly inhibited tumor growth and metastasis. Higher LTBP1 expression is associated with a worse prognosis and advanced stage in bladder cancer patients. In conclusion, this study revealed that LTBP1 may be a potential target for alleviating chemoresistance in bladder cancer.