title: BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder.
abstract: OBJECTIVE
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.|School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan.
authors.forename: I-Wei
authors.initials: IW
authors.lastname: Chang
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Wen-Jen
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan.
authors.forename: Yu-Hui
authors.initials: YH
authors.lastname: Wang
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.
authors.forename: Ting-Feng
authors.initials: TF
authors.lastname: Wu
authors.affiliation: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Peir-In
authors.initials: PI
authors.lastname: Liang
authors.affiliation: Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: He
authors.affiliation: Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan.|Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan.|Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Bi-Wen
authors.initials: BW
authors.lastname: Yeh
authors.affiliation: Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan.|Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan.|National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan.|Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.|Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors.forename: Chien-Feng
authors.initials: CF
authors.lastname: Li
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology*; 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 / Q000032:analysis / Q000096:biosynthesis*; D015854:Up-Regulation; D014571:Urologic Neoplasms / Q000401:mortality / Q000473:pathology*
chemical_list: D014408:Biomarkers, Tumor; C490590:BCAT1 protein, human; D000637:Transaminases
keywords: BCAT1; branched-chain amino acid transaminase 1; upper urinary tract; urinary bladder; urothelial carcinoma