Nuclear β-Catenin Induces an Early Liver Progenitor Phenotype in Hepatocellular Carcinoma and Promotes Tumor Recurrence

Zulehner, Gudrun; Mikula, Mario; Schneller, Doris; Zijl, Franziska van; Huber, Heidemarie; Sieghart, Wolfgang; Grasl‐Kraupp, Bettina; Waldhör, Thomas; Peck‐Radosavljevic, Markus; Beug, Hartmut; Mikulits, Wolfgang

doi:10.2353/ajpath.2010.090300

Cited by 82 publications

(65 citation statements)

References 49 publications

(71 reference statements)

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“…Numerous studies have reported that β-catenin overexpression in the cytoplasm and/or nucleus is correlated with cancer metastasis and poor prognosis (43)(44)(45)(46)(47)(48)(49)(50)(51). In the present study, higher Edmondson grade, poor TNM stage and positive portal vein invasion cases were identified to have increased cytoplasmic expression of β-catenin.…”

Section: Fak β-Catenin C-met Clinicopathological --------------------supporting

confidence: 53%

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Gong

et al. 2018

Oncol Lett

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Abstract. The present study aimed to investigate the prognostic value of specific molecular markers in patients with hepatocellular carcinoma (HCC) who had received surgery. Immunohistochemical analysis was used to measure the expression of hepatocyte growth factor receptor (c-Met), β-catenin and focal adhesion kinase (FAK) in patients with HCC. c-Met expression was identified to be high in patients with larger tumors, higher α-fetoprotein (AFP) levels, higher Edmondson grades, portal vein invasion and higher tumor-node-metastasis (TNM) stages. FAK expression was high in patients with portal vein invasion, higher Edmondson grades and higher TNM stages. β-catenin expression was high in patients with larger tumors, hepatitis B virus (HBV) infection, portal vein invasion, higher Edmondson grades and higher TNM stages. Following multivariate analysis, FAK (P= 0.002) and β-catenin (P= 0.006) expression levels were demonstrated to be significantly associated with Edmondson grade. Additionally, the tumor size (P= 0.009) and HBV infection status (P= 0.002) were revealed to be associated with β-catenin expression. Kaplan-Meier survival curve analysis demonstrated that patients with HCC with higher FAK expression, higher β-catenin expression, portal vein invasion, higher Edmondson grades, higher TNM stages, younger ages and higher AFP levels had significantly poorer prognoses. Cox's regression analysis revealed that the survival period was correlated with the Edmondson grade, age, AFP level, and FAK and β-catenin expression. Univariate analysis of c-Met, β-catenin and FAK identified a significant correlation between FAK and β-catenin (P= 0.015). Correlation analysis revealed no significant correlation between the three molecular markers, but β-catenin and c-Met were markedly correlated (P=0.052). No significant correlation between FAK, c-Met or β-catenin expression was identified. FAK and β-catenin expression demonstrated a correlation with a range of clinicopathological factors, and high FAK and β-catenin expression levels were identified to be correlated with a poor survival rate of patients with HCC. Thus, patients with higher FAK and β-catenin expression may require more aggressive therapy. The results of the present study suggest that FAK and β-catenin expression possess more prognostic value than c-Met expression in patients with HCC.

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Section: Fak β-Catenin C-met Clinicopathological --------------------supporting

confidence: 53%

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Gong

et al. 2018

Oncol Lett

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“…Nuclear localization of β-catenin may also be induced by the TGF-β signaling pathway, in response to trans-differentiation of neoplastic hepatocytes to immature liver progenitor cells. Nuclear expression of β-catenin was correlated with tumor invasion or relapses of HCC following liver transplantation [66].…”

Section: Disturbances In Wnt/β-catenin Pathway In Liver Carcinogenesismentioning

confidence: 99%

“…Involvement of the canonical and non-canonical Wnt pathway in liver oncogenesis has been described by various investigators [59][60][61][62][63][64][65][66][67]. One of the most frequently described mechanisms for activation of the canonical signaling pathway in HCC involves activation of β-catenin through mutations in the CTNNB1 gene.…”

Section: Disturbances In Wnt/β-catenin Pathway In Liver Carcinogenesismentioning

confidence: 99%

Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus

Rogacki¹,

Kasprzak²,

Stępiński³

2015

pjp

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“…Protein expression profiling studies have detected many proteins that are associated with hepatocarcinogenesis. For example, serum level of soluble e-cadherin was shown be elevated in patients with HCC, and is associated with early recurrence or extrahepatic metastasis (12 (17) has been shown to be elevated in patients with HCC and hence could be used as prognostic markers for early detection of HCC. However, limited information is available about the extent to which these proteins could be used as prognostic markers for viral-associated HCC.…”

Section: Introductionmentioning

confidence: 99%

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma

Zekri

Bahnassy²,

El-Din³

et al. 2011

Oncol Rep

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Abstract. the global rising incidence of hepatocellular carcinoma (HCC), which parallels the increase of hepatitis C virus (HCV) prevalence, has sparked a renewed interest in discovering additional HCC serum markers. In this study, we investigated the clinical use of serum e-cadherin, ICAM, MMp-2, VeGF, OpN and β-catenin as potential diagnostic makers for HCV/genotype 4-associated HCC. twenty cases of healthy subjects, 11 cases with asymptomatic HCV/genotype 4 carriers (AsC), 28 chronic hepatitis (CH) cases and 32 patients with HCC were enrolled in this study. serum levels of proteins were measured by a sandwich-enzyme-linked (eLIsA) assay. the diagnostic accuracy of each candidate marker was evaluated using receiver-operating characteristic (rOC) curve analysis, reporting the area under the curve (AUC) and its 95% confidence interval (CI). We demonstrated that serum β-catenin levels were significantly elevated in patients with HCC compared to those with CH, AsC and healthy controls. Among the six studied markers, β-catenin was also found to be the only marker that can significantly discriminate between patients with HCC and those with CH; therefore, β-catenin could be considered as a potential marker for early diagnosis of HCV-associated HCC in patients infected with HCV genotype 4. IntroductionHepatocellular carcinoma (HCC) is the fifth most common cancer and one of the leading causes of cancer death in the world (1). It has heterogeneous geographical distribution, with its greatest incidence in Asia and sub-saharan Africa, where hepatitis B infection is endemic (2). Its incidence has also been increasing steadily in the United states and Western europe due to the high prevalence of hepatitis C (3,4). egypt has the highest prevalence of hepatitis C virus (HCV) infection, with 14% of the population infected and seven million with chronic liver hepatitis (5,6). Little is known about the molecular mechanisms by which HCV initiates HCC. Molecular studies directed at mapping the etiology of HCV disease progression to HCC are expected to provide new insights on the management of this increasing problem and hence are of great global health interest. However, the lack of molecular makers that can characterize the stage of HCC, regardless of the etiologic factor, and tumor progression precludes the effective diagnosis and prognosis of HCC. Currently, HCC diagnosis relies on the radiology imaging systems, and elevated serum α-fetoprotein (AFp). serum AFp is not always elevated to a diagnostic level in all patients in small HCC, thus, considerable numbers of patients with more advanced stages would be missed unless other diagnostic tools are used (7,8). Moreover, the level of AFp may be elevated in non-malignant chronic liver diseases, including chronic hepatitis and cirrhosis (9,10). several biomarkers, such as des-γ-carboxyprothrombin/prothrombin induced by vitamin K absence-II, lens cularis agglutininreactive (AFp-L3), and glypican-3, have been examined for their ability to diagnose early HCC (11). However, there is a...

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Nuclear β-Catenin Induces an Early Liver Progenitor Phenotype in Hepatocellular Carcinoma and Promotes Tumor Recurrence

Cited by 82 publications

References 49 publications

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Prognostic significance of c-Met, β-catenin and FAK in patients with hepatocellular carcinoma following surgery

Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus

Serum levels of β-catenin as a potential marker for genotype 4/hepatitis C-associated hepatocellular carcinoma

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