Prognostic Significance of Beta-Catenin Expression in Patients with Esophageal Carcinoma: a Meta-analysis

Zeng, Rong; Duan, Lei; Kong, Yuke; Wu, Xiaolu; Wang, Ya; Xin, Gang; Yang, Kun

doi:10.7314/apjcp.2014.15.15.6103

Cited by 8 publications

(5 citation statements)

References 45 publications

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“…While our results suggested that CDH1 or CTNNB1 expression alone did not affect the prognosis of patients, whether CDH1 and CTNNB1 expression may serve as a good prognostic marker in esophageal cancer is still controversial. In the meta-analysis, there are two reports that CDH1 expression alone is a valid prognostic marker [36] and aberrant CTNNB1 alone is a prognostic factor [37]. Our data suggested that CDH alone or CTNNB1 alone did not affect the prognosis of the patients with esophageal cancer, though we could not clarify the discrepancy between their data and ours.…”

Section: Discussioncontrasting

confidence: 89%

Decreased expression of CDH1 or CTNNB1 affects poor prognosis of patients with esophageal cancer

et al. 2016

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BackgroundE-cadherin/CDH1 is one of the proteins involved in cell adhesion, and it is known that decreased expression of E-cadherin induces lymph node metastasis in esophageal cancer. Beta catenin/CTNNB1, which is an important component of the Wnt signaling pathway, binds to E-cadherin at the cell membrane, where the complex of these two proteins functions in the stabilization of cell adhesion. However, its role in the pathogenesis of esophageal cancer is still unknown.MethodsThis study included 86 patients with esophageal cancer who underwent surgery between 1998 and 2007. The expression of the E-cadherin/CDH1 gene product (E-cadherin/CDH1) and that of the beta catenin/CTNNB1 protein in the cell membrane were analyzed by immunohistochemistry. We examined the correlations among CDH1 or CTNNB1 expression, clinicopathological factors, and the prognosis of patients with ESCC.ResultsCDH1 and CTNNB1 were expressed in 52.3 % (45/86) and 36.0 % (31/86) of tumor samples, respectively. Both CDH1 and CTNNB1 were co-expressed in 22.1 % (19/86) of esophageal cancer tissues. CDH1 expression correlated with the p-stage (stages I–II vs stages III–IV, p = 0.032), T factor (T1–2 vs T3–4, p = 0.0088), and lymphatic invasion (p = 0.019). However, CDH1 expression did not correlate with the N factor or the blood vessel invasion. CTNNB1 expression correlated with the T factor (T1–2 vs T3–4, p = 0.0015), p-stage (stages I–II vs stages III–IV, p = 0.030), and lymphatic invasion (p = 0.007). The CDH1(+)/CTNNB1(+) phenotype was inversely correlated with the T factor, N factor, p-stage, lymphatic invasion, and blood vessel invasion. Furthermore, patients whose tumors were double-positive for CDH1 and CTNNB1 had a significantly higher survival rate than those whose tumors were negative for CDH1 or CTNNB1 (log-rank test, p = 0.0192). The T factor and N factor had a strong negative correlation with double-positive tumors. These were both independent prognostic factors, as was the double-positive phenotype. A univariate analysis indicated that the T factor, the N factor, and CDH1 and CTNNB1 co-expression were significant variables that predicted survival (hazard ratio, 2.387; 95 % confidence interval, 1.115–5.102; p = 0.025).ConclusionsDecreased expression of CDH1 or CTNNB1 in the cell membranes of cancer cells is associated with poor survival of patients with esophageal cancer.

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Section: Discussioncontrasting

confidence: 89%

Decreased expression of CDH1 or CTNNB1 affects poor prognosis of patients with esophageal cancer

et al. 2016

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“…Li et al (9) revealed that aberrant expression of β-catenin, which was defined as "reduced expression in membrane" or "overexpression in cytoplasm/ nucleus", significantly influenced the survival of patients with gastric cancer (HR: 1.85; 95% CI: 1.39-2.46). Zeng et al (52) also suggested that altered expression of β-catenin could serve as a predicative factor of poor prognosis for patients with esophageal carcinoma. Zhang et al (50) and Chen et al (53) have demonstrated that positive β-catenin expression in cytoplasm/nucleus was significantly associated with poor prognosis of breast cancer and hepatocellular carcinoma respectively.…”

Section: Discussionmentioning

confidence: 99%

Prognostic significance of β-catenin expression in patients with non-small cell lung cancer: a meta-analysis

Jin

Zhan

Katoh

et al. 2017

Transl. Lung Cancer Res.

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Reduced membranous β-catenin, positive expression of cytoplasmic or nuclear β-catenin is all correlated with poor prognosis, although we did not identify a significant association between abnormal β-catenin expression and clinical outcome of NSCLC patients. The meta-analysis suggested that membranous, cytoplasmic and nuclear β-catenin all could serve as an important prognosticator for patients with NSCLC.

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“…Previous meta-analyses have proven that nuclear β-catenin overexpression predicts progressive disease and unfavorable survival in colorectal cancer [25], lung cancer [26, 27], hepatocellular cancer [28], breast cancer [29], esophageal cancer [30], and gastric cancer [31]. As the prognostic value of β-catenin in pancreatic cancer remains controversial, a meta-analysis was needed to explore the issue clearly.…”

Section: Discussionmentioning

confidence: 99%

FH535, a β-catenin pathway inhibitor, represses pancreatic cancer xenograft growth and angiogenesis

et al. 2016

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The WNT/β-catenin pathway plays an important role in pancreatic cancer carcinogenesis. We evaluated the correlation between aberrant β-catenin pathway activation and the prognosis pancreatic cancer, and the potential of applying the β-catenin pathway inhibitor FH535 to pancreatic cancer treatment. Meta-analysis and immunohistochemistry showed that abnormal β-catenin pathway activation was associated with unfavorable outcome. FH535 repressed pancreatic cancer xenograft growth in vivo. Gene Ontology (GO) analysis of microarray data indicated that target genes responding to FH535 participated in stemness maintenance. Real-time PCR and flow cytometry confirmed that FH535 downregulated CD24 and CD44, pancreatic cancer stem cell (CSC) markers, suggesting FH535 impairs pancreatic CSC stemness. GO analysis of β-catenin chromatin immunoprecipitation sequencing data identified angiogenesis-related gene regulation. Immunohistochemistry showed that higher microvessel density correlated with elevated nuclear β-catenin expression and unfavorable outcome. FH535 repressed the secretion of the proangiogenic cytokines vascular endothelial growth factor (VEGF), interleukin (IL)-6, IL-8, and tumor necrosis factor-α, and also inhibited angiogenesis in vitro and in vivo. Protein and mRNA microarrays revealed that FH535 downregulated the proangiogenic genes ANGPT2, VEGFR3, IFN-γ, PLAUR, THPO, TIMP1, and VEGF. FH535 not only represses pancreatic CSC stemness in vitro, but also remodels the tumor microenvironment by repressing angiogenesis, warranting further clinical investigation.

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Prognostic Significance of Beta-Catenin Expression in Patients with Esophageal Carcinoma: a Meta-analysis

Cited by 8 publications

References 45 publications

Decreased expression of CDH1 or CTNNB1 affects poor prognosis of patients with esophageal cancer

Decreased expression of CDH1 or CTNNB1 affects poor prognosis of patients with esophageal cancer

Prognostic significance of β-catenin expression in patients with non-small cell lung cancer: a meta-analysis

FH535, a β-catenin pathway inhibitor, represses pancreatic cancer xenograft growth and angiogenesis

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