Wnt-1 protein as a prognostic biomarker for hepatitis B-related and hepatitis C-related hepatocellular carcinoma after surgery.
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 semiquantitatively 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 I) and 37 (group II) HCC patients had an expression ratio of Wnt-1 > or =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.
Department of Medical Research, Chi-Mei Medical Center, Tainan 710, Taiwan.
Hao-Hsien
HH
Lee
Yih-Huei
YH
Uen
Yu-Feng
YF
Tian
Chi-Shu
CS
Sun
Ming-Jen
MJ
Sheu
Hsing-Tao
HT
Kuo
Lok-Beng
LB
Koay
Ching-Yih
CY
Lin
Ching-Cherng
CC
Tzeng
Chia-Ju
CJ
Cheng
Ling-Yu
LY
Tang
Sun-Lung
SL
Tsai
Andrew H-J
AH
Wang
D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor; D015153:Blotting, Western; D015820:Cadherins / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000601:surgery / Q000821:virology*; D005260:Female; D006509:Hepatitis B / Q000150:complications*; D006526:Hepatitis C / Q000150:complications*; D006801:Humans; D007124:Immunoenzyme Techniques; D008113:Liver Neoplasms / Q000601:surgery / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D051155:Wnt1 Protein / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism
D014408:Biomarkers, Tumor; D015820:Cadherins; D051155:Wnt1 Protein; D051176:beta Catenin