Abstract
BackgroundThe 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.MethodsSystematic 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).ResultsA 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.ConclusionsCytoplasmic 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.
Highlights
Hepatocellular cancer (HCC) is a global health problem and its incidence has been increasing dramatically since 20 years especially in developed countries [1]
The terms used in search was as follows:‘‘b-catenin, Beta-catenin, or CTNNB1’’, ‘‘WNT/bcatenin signal pathway’’, "prognostic, prognosis, or survival", ‘‘HCC’’, ‘‘hepatocellular carcinoma’’, ‘‘hepatic tumor’’, ‘‘hepatic cancer’’, ‘‘liver cancer’’, ‘‘liver tumor’’ and ‘‘liver neoplasms’’ with all possible combinations
Criteria for Inclusion and Exclusion To make this meta-analysis meet the high standards, studies had to fulfill the following criteria: (1) patients with distinctive hepatocellular carcinoma diagnosis by pathology but without restriction on age or ethnicity; (2) b-catenin expression was measured by immunohistological chemistry (IHC) or other methods in primary HCC tissue; (3) clinical trials or reports were published in English; (4) sufficient information or valid data about b-catenin expression and overall survival (OS) or recurrence-free survival (RFS) and the other clinicopathological features were provided directly or could be calculated indirectly; (5) the study with the highest quality assessment was enrolled when several studies reported by one individual author were conducted on the same patients population; (6) the patients were followed-up for at least 3 years
Summary
Hepatocellular cancer (HCC) is a global health problem and its incidence has been increasing dramatically since 20 years especially in developed countries [1]. In 2012, it was reported that its annual incidence reached more than half a million worldwide [2] It ranks No three on the most frequent cause of cancer-related death list among the global population [3]. The b-catenin is an important effector in WNT/b-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 b-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. No consensus was obtained on the prognostic and clinicopathological significance of cytoplasmic/nuclear b-catenin overexpression for HCCs
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