BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder

I. Wei Chang, Wen Jen Wu, Yu Hui Wang, Ting Feng Wu, Peir In Liang, Hong Lin He, Bi Wen Yeh, Chien Feng Li

Research output: Contribution to journalArticle

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)520-532
Number of pages13
JournalHistopathology
Volume68
Issue number4
DOIs
Publication statusPublished - Mar 1 2016
Externally publishedYes

Fingerprint

Urinary Tract
Urinary Bladder
Carcinoma
Neoplasm Metastasis
Amino Acids
Neoplasms
Proteins
Data Mining
Survival
branched-chain-amino-acid transaminase
Reverse Transcription
Carcinogenesis
Multivariate Analysis
Biomarkers
Databases
Polymerase Chain Reaction
Genes

Keywords

  • BCAT1
  • Branched-chain amino acid transaminase 1
  • Upper urinary tract
  • Urinary bladder
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology

Cite this

BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. / Chang, I. Wei; Wu, Wen Jen; Wang, Yu Hui; Wu, Ting Feng; Liang, Peir In; He, Hong Lin; Yeh, Bi Wen; Li, Chien Feng.

In: Histopathology, Vol. 68, No. 4, 01.03.2016, p. 520-532.

Research output: Contribution to journalArticle

Chang, I. Wei ; Wu, Wen Jen ; Wang, Yu Hui ; Wu, Ting Feng ; Liang, Peir In ; He, Hong Lin ; Yeh, Bi Wen ; Li, Chien Feng. / BCAT1 overexpression is an indicator of poor prognosis in patients with urothelial carcinomas of the upper urinary tract and urinary bladder. In: Histopathology. 2016 ; Vol. 68, No. 4. pp. 520-532.
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AU - Wu, Wen Jen

AU - Wang, Yu Hui

AU - Wu, Ting Feng

AU - Liang, Peir In

AU - He, Hong Lin

AU - Yeh, Bi Wen

AU - Li, Chien Feng

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N2 - 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.

AB - 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.

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