Abstract

The role and molecular mechanisms of branched-chain amino acid (BCAA) metabolism in bladder urothelial carcinoma (BLCA) have not been fully elucidated. In this study, genes associated with BCAA metabolism were identified and analysed. Based on the TCGA-BLCA dataset, BCAA metabolism-related clusters were established. The analysis revealed significant differences among clusters in terms of survival outcomes, biological functions, and immune infiltration. Hub genes were identified using Cox and LASSO regression analyses, leading to the construction of a four-gene prognostic model that included BCAT1. Patients were categorised into high- and low-risk groups, with the high-risk group showing a markedly higher risk of mortality. Key module genes were determined through weighted gene coexpression network analysis, and BCAT1 was ultimately identified as the core gene involved in BCAA metabolism. High BCAT1 expression was strongly associated with poor prognosis. Single-cell RNA sequencing data revealed that BCAT1 was highly expressed in malignant epithelial cells and correlated with the immune microenvironment. Experimental validation demonstrated that BCAA uptake and metabolism were enhanced in BLCA and that BCAT1 upregulation promoted tumour progression and epithelial-mesenchymal transition by activating the PI3K/AKT/mTOR pathway. Molecular docking and virtual screening further identified folic acid as a compound capable of binding to the BCAT1 protein and inhibiting the migration and invasion of BLCA cells. In conclusion, this study demonstrates that BCAT1 plays a pivotal role in BLCA progression by regulating the PI3K/AKT/mTOR pathway, suggesting its potential as a novel therapeutic target for BLCA.