國家衛生研究院 NHRI:Item 3990099045/8200
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    题名: AMACR overexpression is associated with clinical and biological aggressiveness in urothelial carcinomas of the upper urinary tract and urinary bladder
    作者: Li, CF;Wu, WJ;Huang, CN;Li, CC;Ke, HL;Li, WM;Yeh, HC;Lee, YY;Lin, HH;Yeh, BW;Hwang, SJ;Liang, PI
    贡献者: National Institute of Cancer Research
    摘要: Background: Alpha-methylacyl CoA racemase (AMACR) is essential for catabolism of branched-chain fatty acids, allowing their subsequent b-oxidation to generate energy. However, its significance has not been assessed in urothelial carcinoma. We therefore analysed the clinicopathological and biological significance of AMACR expression in urothelial carcinoma. Methods: Laser capture microdissection coupled with real-time qRT-PCR was used to detect AMACR transcript level in 22 urothelial carcinomas of the urinary bladder. Immunohistochemistry evaluated by using H-score was used to determine AMACR protein expression in 295 urothelial carcinomas of the urinary bladder and 340 urothelial carcinomas of the upper urinary tract. mRNA and protein expression were correlated with clinicopathological features. AMACR protein expression was further evaluated for associations with disease-specific survival (DSS) and metastasis-free survival (MeFS). In vitro, AMACR overexpressing urothelial carcinoma cell lines (BFTC905 and RTCC-1) were evaluated for its biological function using RNA interference. Findings: Increments of AMACR transcript level was associated with higher pT status (p = 0.017). AMACR protein overexpression was significantly associated with advanced pT status (both p < 0.001), nodal metastasis (both p 6 0.001), high histological grade (both p 6 0.001), vascular invasion (urothelial carcinomas of the upper urinary tract, p < 0.001; urothelial carcinomas of the urinary bladder, p = 0.003), frequent mitoses (urothelial carcinomas of the upper urinary tract, p = 0.007; urothelial carcinomas of the urinary bladder, p < 0.001) in both groups of urothelial carcinomas. AMACR overexpression not only predicted worse DSS and MeFS at univariate analysis, but was also associated with inferior DSS (urothelial carcinomas of the upper urinary tract, p = 0.025; urothelial carcinomas of the urinary bladder, p = 0.001) and MeFS (urothelial carcinomas of the upper urinary tract, p = 0.028; urothelial carcinomas of the urinary bladder, p = 0.019) in multivariate analysis. In both urothelial carcinoma cell lines, stable AMACR knockdown resulted in impaired cell proliferation, as well as migration/invasion capabilities. Interpretation: AMACR overexpression is associated with advanced clinical features for patients with urothelial carcinoma and may serve as a potential prognostic biomarker and a novel therapeutic target.
    日期: 2014-05
    關聯: European Journal of Cancer. 2014 May;50(Suppl. 4):e35.
    Link to: http://dx.doi.org/10.1016/j.ejca.2014.03.137
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0959-8049&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000351589200098
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