Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

Li, Lifu; Wei, Zhengjie; Sun, Hong; Jiang, Bo

doi:10.3748/wjg.v20.i34.12313

Cited by 31 publications

(21 citation statements)

References 39 publications

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“…Dysregulation of Wnt/β-catenin Signaling in Gastrointestinal Cancers As a central molecule in the Wnt signaling pathway, β-catenin is in the membrane, cytoplasm and nucleus. Cytoplasmic and nuclear expressions are mainly involved in the regulation of the Wnt signaling path (Li et al, 2014). When the accumulation of β-catenin occurs in the nucleus there is activation of the E-cadherin, loss target gene expression program, linking the epithelial-mesenchymal transition to the Wnt signaling pathway (White et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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Colorectal cancer (CRC) is one of the most frequent neoplasms worldwide, and up to 15% have a family history. Lynch syndrome (LS) is a hereditary cause of CRC and gastric (GC). Individuals with LS have mutations in mismatch genes repair. p53, cyclin D1, β-catenin, APC and c-myc proteins are involved in the cell cycle and carcinogenesis. Objective: To study the expression of p53, Cyclin D1, β-catenin, APC and c-myc proteins in patients with CRC and GC with at least one of the Bethesda positive criteria. Compare the expression of these proteins with the presence or absence of expression of the DNA repair proteins. Patients and Methods: We included 70 individuals with CRC or GC with at least one of the Bethesda positive criteria. Protein expression of MLH1, MSH2, MSH6, PMS2, p53, cyclin D1, β-catenin, APC and c-myc were analized by immunohistochemistry tumours tissues. Results: Deficient expression of MLH1, MSH2, MSH6 and PMS2 were respectively 38.7%; 17.7%; 26.22% and 48.38%. We found a negative association between deficiency of PMS2 and age, and positive association between PMS2 deficiency and APC positive. The positive imunoexpression of APC increases by 4 times the chance of having deficiency of PMS2. Conclusions: Patients with loss of expression of PMS2 had a higher risk of mutation or deletion of APC and tumours with positive immunoexpression of cyclin D1 had an increased risk of loss of expression of MSH2. These results suggest that tumours with loss of expression of DNA repair proteins had a higher loss of cell control cycle.

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Section: Discussionmentioning

confidence: 99%

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

Marcolino

Pimenta

Neto

et al. 2020

Asian Pac J Cancer Prev

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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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“…β-catenin exerts dual distinct roles depending on its intracellular localization. β-catenin expressed on the membrane binds tightly to classical cadherins, regulates cell-to-cell adhesion and cell growth, and has a negative effect on tumor growth (9). Cytoplasmic and nuclear β-catenin mainly acts as a central molecule in Wingless family (Wnt) signaling pathway (10).…”

Section: Introductionmentioning

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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Abnormal β-catenin immunohistochemical expression as a prognostic factor in gastric cancer: A meta-analysis

Abstract: Abnormal β-catenin immunohistochemical expression may be associated with tumor progression and could be a predictive factor of poor prognosis in patients with GC.

Cited by 31 publications

References 39 publications

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

p53, Cyclin-D1, β-catenin, APC and c-myc in Tumor Tissue from Colorectal and Gastric Cancer Patients with Suspected Lynch Syndrome by the Bethesda Criteria

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

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

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