I-Wei Chang1,2, Wen-Jen Wu3,4,5,6,7, Yu-Hui Wang8, Ting-Feng Wu9, Peir-In Liang10, Hong-Lin He1, Bi-Wen Yeh3,4,5,6,7, Chien-Feng Li9,11,12,13,14. 1. Department of Pathology, E-DA Hospital, I-Shou University, Kaohsiung, Taiwan. 2. School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan. 3. Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 4. Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 5. Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan. 6. Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung, Taiwan. 7. Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung, Taiwan. 8. Institute of Bioinformatics and Biosignal Transduction, National Cheng Kung University, Tainan, Taiwan. 9. Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan. 10. Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan. 11. Department of Pathology, Chi-Mei Medical Center, Tainan, Taiwan. 12. National Cancer Research Institute, National Health Research Institutes, Tainan, Taiwan. 13. Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. 14. Department of Internal Medicine and Cancer Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
Abstract
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.
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.
Authors: Aurélie Mbeutcha; Morgan Rouprêt; Ashish M Kamat; Pierre I Karakiewicz; Nathan Lawrentschuk; Giacomo Novara; Jay D Raman; Christian Seitz; Evanguelos Xylinas; Shahrokh F Shariat Journal: World J Urol Date: 2016-04-21 Impact factor: 4.226
Authors: V Thewes; R Simon; M Hlevnjak; M Schlotter; P Schroeter; K Schmidt; Y Wu; T Anzeneder; W Wang; P Windisch; M Kirchgäßner; N Melling; N Kneisel; R Büttner; U Deuschle; H P Sinn; A Schneeweiss; S Heck; S Kaulfuss; H Hess-Stumpp; J G Okun; G Sauter; A E Lykkesfeldt; M Zapatka; B Radlwimmer; P Lichter; M Tönjes Journal: Oncogene Date: 2017-03-20 Impact factor: 9.867
Authors: Aurélie Mbeutcha; Romain Mathieu; Morgan Rouprêt; Kilian M Gust; Alberto Briganti; Pierre I Karakiewicz; Shahrokh F Shariat Journal: Transl Androl Urol Date: 2016-10