Cytoplasmic and/or nuclear expression of β-catenin correlate with poor prognosis and unfavorable clinicopathological factors in hepatocellular carcinoma: a meta-analysis.
BACKGROUND
The β-catenin is an important effector in WNT/β-catenin signaling pathway, which exerts a crucial role in the development and progression of hepatocellular carcinoma (HCC). Some researchers have suggested that the overexpression of β-catenin in cytoplasm and/or nucleus was closely correlated to metastasis, poor differentiation and malignant phenotype of HCC while some other researchers hold opposite point. So far, no consensus was obtained on the prognostic and clinicopathological significance of cytoplasmic/nuclear β-catenin overexpression for HCCs.


METHODS
Systematic strategies were applied to search eligible studies in all available databases. Subgroup analyses, sensitivity analyses and multivariate analysis were performed. In this meta-analysis, we utilized either fixed- or random-effects model to calculate the pooled odds ratios (OR) and its 95% confidence intervals (CI).


RESULTS
A total of 22 studies containing 2334 cases were enrolled in this meta-analysis. Pooled data suggested that accumulation of β-catenin in cytoplasm and/or nucleus significantly correlated with poor 1-, 3- and 5-year OS and RFS. Moreover, nuclear accumulation combined with cytoplasmic accumulation of β-catenin tended to be associated with dismal metastasis and vascular invasion while cytoplasmic or nuclear expression alone showed no significant effect. Besides, no significant association was observed between cytoplasmic and/or nuclear β-catenin expression and poor differentiation grade, advanced TNM stage, liver cirrhosis, tumor size, tumor encapsulation, AFP and etiologies. Additional subgroup analysis by origin suggested that the prognostic value and clinicopathological significance of cytoplasmic and/or nuclear β-catenin expression was more validated in Asian population. Multivariate analyses of factors showed that cytoplasmic and/or nuclear β-catenin expression, as well as TNM stage, metastasis and tumor size, was an independent risk factors for OS and RFS.


CONCLUSIONS
Cytoplasmic and/or nuclear accumulation of β-catenin, as an independent prognostic factor, significantly associated with poor prognosis and deeper invasion of HCC, and could serve as a valuable prognostic predictor for HCC.
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Jiang
J
Chen
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Jinghua
J
Liu
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Renan
R
Jin
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Jiliang
J
Shen
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Yuelong
Y
Liang
Department of Surgery, Zhejiang University Hospital, Hangzhou, Zhejiang, China.
Rui
R
Ma
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Hui
H
Lin
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Xiao
X
Liang
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Hong
H
Yu
Department of General Surgery, Sir Run Run Shaw Hospital of Zhejiang University, Hangzhou, Zhejiang, China.
Xiujun
X
Cai
D014408:Biomarkers, Tumor / Q000378:metabolism; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D015870:Gene Expression; D006801:Humans; D008103:Liver Cirrhosis; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality* / Q000473:pathology; D060787:Neoplasm Grading; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D016017:Odds Ratio; D047368:Tumor Burden; D000509:alpha-Fetoproteins / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D014408:Biomarkers, Tumor; D000509:alpha-Fetoproteins; D051176:beta Catenin