AIMS: Amino acid biosynthesis is one of the cardinal events of carcinogenesis that has not been investigated in urothelial carcinoma (UC). By data mining a published transcriptomic database of UCs of urinary bladder (UBUCs) (GSE31684), we identified branched-chain amino acid transaminase 1 (BCAT1) as the most significantly stepwise upregulated gene during tumor progression among those associated with amino acid biosynthetic process (GO:0008652). Accordingly, we analyzed BCAT1 transcript and protein expression with their clinicopathological significance. METHODS AND RESULTS: We used real time RT-PCR to detect BCAT1 transcript levels in 20 UCs of upper tract (UTUCs) and 20 UBUCs, respectively. Immunohistochemical study was performed to determine BCAT1 protein expression in 340 UTUCs and 295 UBUCs. Higher BCAT1 transcript levels were associated with higher pT status in both groups (p<0.05). BCAT1 protein overexpression was also significantly associated with adverse clinicopathological features, e.g., advanced pT stage, nodal metastasis, high pathological grade and etc. (p<0.05). BCAT1 overexpression predicted worse disease-specific survival and metastasis-free survival in both univariate and multivariate analyses (p</=0.001). CONCLUSION: BCAT1 overexpression is associated with advanced tumor status, and implies adverse clinical outcomes of UCs, suggesting its role in tumor progression and could serve as a prognostic biomarker and a novel therapeutic target in UC.
