Wnt-1 Protein as a Prognostic Biomarker for Hepatitis B-Related and Hepatitis C-Related Hepatocellular Carcinoma after Surgery

被引:29
作者
Lee, Hao-Hsien
Uen, Yih-Huei [1 ]
Tian, Yu-Feng [1 ]
Sun, Chi-Shu [2 ]
Sheu, Ming-Jen [2 ]
Kuo, Hsing-Tao [2 ]
Koay, Lok-Beng [2 ]
Lin, Ching-Yih [2 ]
Tzeng, Ching-Cherng [3 ]
Cheng, Chia-Ju [4 ]
Tang, Ling-Yu [4 ]
Tsai, Sun-Lung [2 ,4 ]
Wang, Andrew H-J. [5 ,6 ]
机构
[1] Chi Mei Med Ctr, Dept Gen Surg, Tainan, Taiwan
[2] Chi Mei Med Ctr, Dept Internal Med, Tainan, Taiwan
[3] Chi Mei Med Ctr, Dept Pathol, Tainan, Taiwan
[4] Chi Mei Med Ctr, Dept Med Res, Tainan, Taiwan
[5] Acad Sinica, Inst Biol Chem, Taipei, Taiwan
[6] Acad Sinica, Core Facil Prote Res, Taipei, Taiwan
关键词
BETA-CATENIN MUTATIONS; NF-KAPPA-B; INTRAHEPATIC RECURRENCE; GENE-EXPRESSION; E-CADHERIN; VIRUS; PATHWAY; ACTIVATION; HEPATOCARCINOGENESIS; PATHOGENESIS;
D O I
10.1158/1055-9965.EPI-09-0039
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Up-regulation of Wnt-1 protein has been reported in hepatitis B virus (HBV)-related and hepatitis C virus (HCV)-related hepatocellular carcinoma (HCC) tissues and cell lines. It is known to play a fundamental role in signaling cancer progression, whereas its prognostic role in HCC remains unexplored. Methods: As a prognostic biomarker, this study analyzed Wnt-1 protein expression in 63 histology-verified HCC patients receiving curative resection. In each paired tumor and nontumor specimen, Wnt-1 levels were semi quantitatively measured by Western blotting and expressed by tumor/nontumor ratio. The data were further correlated with quantitative real-time PCR as well as with beta-catenin and E-cadherin expression by immunohistochemistry. Cumulative tumor recurrence-free survival curves were constructed using the Kaplan-Meier method and compared by the log-rank test. Results: The results showed that 26 (group 1) and 37 (group 11) HCC patients had an expression ratio of Wnt-1 >= 1.5 and <1.5, respectively. The amount of Wnt-1 estimated by tumor/nontumor ratio correlated with the results by quantitative real-time PCR. High tumor Wnt-1 expression correlated with enhanced nuclear beta-catenin accumulation, diminished membranous E-cadherin expression, and increased tumor recurrence after curative tumor resection. Conclusions: These results suggest that Wnt-1 may be used as a predisposing risk factor for HCC recurrence. The use of tumor Wnt-1 as prognostic biomarker may identify patients with HBV- and/or HCV-related HCC patients with a high risk of tumor recurrence who may then benefit from further intensive therapy after surgery. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1562-9)
引用
收藏
页码:1562 / 1569
页数:8
相关论文
共 56 条
[1]  
Bartlett D, 2005, CANC PRINCIPLES PRAC, P986
[2]   Functional interaction of beta-catenin with the transcription factor LEF-1 [J].
Behrens, J ;
vonKries, JP ;
Kuhl, M ;
Bruhn, L ;
Wedlich, D ;
Grosschedl, R ;
Birchmeier, W .
NATURE, 1996, 382 (6592) :638-642
[3]   Molecular viral oncology of hepatocellular carcinoma [J].
Block, TM ;
Mehta, AS ;
Fimmel, CJ ;
Jordan, R .
ONCOGENE, 2003, 22 (33) :5093-5107
[4]  
Bournat JC, 2000, J NEUROSCI RES, V61, P21, DOI 10.1002/1097-4547(20000701)61:1<21::AID-JNR3>3.0.CO
[5]  
2-7
[6]   Signal transduction cascades and hepatitis B and C related hepatocellular carcinoma [J].
Branda, M ;
Wands, JR .
HEPATOLOGY, 2006, 43 (05) :891-902
[7]   Management of hepatoceullular carcinoma [J].
Bruix, J ;
Sherman, M .
HEPATOLOGY, 2005, 42 (05) :1208-1236
[8]   Wnt signaling: complexity at the surface [J].
Cadigan, KM ;
Liu, YI .
JOURNAL OF CELL SCIENCE, 2006, 119 (03) :395-402
[9]  
CARDIGAN KM, 1997, GENE DEV, V11, P3286
[10]   Hepatitis B virus X protein is essential for the activation of Wnt/β-catenin signaling in hepatoma cells [J].
Cha, MY ;
Kim, CM ;
Park, YM ;
Ryu, WS .
HEPATOLOGY, 2004, 39 (06) :1683-1693