BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.
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 up-regulated gene during tumour progression among those associated with the amino acid biosynthetic process (GO:0008652). Accordingly, we analysed BCAT1 transcript and protein expression with their clinicopathological significance.


METHODS AND RESULTS
We used real-time reverse transcription-polymerase chain reaction (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 associated significantly with adverse clinicopathological features, e.g. advanced pT stage, nodal metastasis, high pathological grade, 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 tumour status, and implies adverse clinical outcomes of UCs, suggesting that its role in tumour progression could serve as a prognostic biomarker and a novel therapeutic target in UC.
['Chang|I-Wei|IW|', 'Wu|Wen-Jen|WJ|', 'Wang|Yu-Hui|YH|', 'Wu|Ting-Feng|TF|', 'Liang|Peir-In|PI|', 'He|Hong-Lin|HL|', 'Yeh|Bi-Wen|BW|', 'Li|Chien-Feng|CF|']
D000368:Aged D014408:Biomarkers, Tumor D015153:Blotting, Western D002295:Carcinoma, Transitional Cell D018450:Disease Progression D018572:Disease-Free Survival D005260:Female D006801:Humans D007150:Immunohistochemistry D053208:Kaplan-Meier Estimate D008297:Male D008875:Middle Aged D011379:Prognosis D060888:Real-Time Polymerase Chain Reaction D000637:Transaminases D015854:Up-Regulation D014571:Urologic Neoplasms
BCAT1 urothelial carcinoma upper urinary tract urinary bladder branched-chain amino acid transaminase 1