Wnt/β-catenin pathway as a potential prognostic and predictive marker in patients with advanced ovarian cancer

Abstract

Backgroundβ-catenin is the key protein in the WNT signalling pathway and it forms adherent junctions together with E-cadherin. In ovarian carcinoma, abnormal expression of β-catenin, E-cadherin and WNT-1 was observed, but their prognostic and predictive role is unclear. The aim of this study was to clarify the prognostic and predictive role of E-cadherin, β-catenin and WNT-1 in advanced epithelial ovarian carcinoma (AEOC).MethodsThe expression of E-cadherin, β-catenin and WNT-1 was determined by immunohistochemistry in AEOC. The correlation between expression of these proteins and progression-free survival (PFS) and overall survival (OS) was evaluated. Statistical analyses included Kaplan-Meier estimation, log-rank test, Spearman correlation and Cox proportional-hazards model.ResultsIn ovarian cancer, intense expression of E-cadherin, β-catenin and WNT-1 was found. In multivariate analysis, strong membrane β-catenin expression was an independent unfavourable predictor for PFS (HR 2.19, 95% CI 1.09-4.39; p = 0.028), while in univariate analysis, strong membrane β-catenin expression was a prognostic factor for OS in patients with AOC (p = 0.039). In multivariate analysis, only resistance to first-line chemotherapy was an adverse independent prognostic factor for OS (HR 16.84; 95% CI 5.07-55.98; p < 0.0001). Additionally, strong membranous β-catenin expression was associated with resistance to platinum-based chemotherapy (p = 0.027).ConclusionsThese findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

The role of reproductive hormones in epithelial ovarian carcinogenesis

“…Various signaling pathways have been implicated in gonadotropin-induced proliferation, invasion, and metastasis formation in ovarian cancer, such as the RAS/RAF/ MAPK/ERK (Pilarski et al 2012, Hilliard et al 2013, Smolle et al 2013, PI3K/PTEN/AKT/mTOR (Cancer Genome Atlas Research Network 2011, Huang et al 2011, Yamamoto et al 2011, 2012, Carden et al 2012, Abe et al 2013, Dobbin & Landen 2013, and Wnt/ b-catenin signaling pathways (Bodnar et al 2014, Ford et al 2014, Qi et al 2014. Gonadotropin (FSH and LH) receptors share various downstream signaling pathways, including PI3K and MAPK, and consequently, the potential crosstalk between gonadotropins and molecular pathway signaling is of great interest in exploring targeted cancer therapies.…”

β-Catenin expression is regulated by an IRES-dependent mechanism and stimulated by paclitaxel in human ovarian cancer cells

“…However, the role of the Wnt pathway in the various OC subtypes remains undefined, partly because of its diverse mechanisms of activation in OC [8]. Indeed, bcatenin mutation is mainly confined to endometrioid adenocarcinomas [9] where it is predominantly expressed in the nucleus; it is at the "heart" of the Wnt/b-catenin pathway and activates the expression of many important proteins responsible for the cell cycle, proliferation, and survival, such as cyclin D1 and c-myc [10].…”

Correlation Between E-cadherin Immunoexpression and Efficacy of First Line Platinum-Based Chemotherapy in Advanced High Grade Serous Ovarian Cancer

“…β-catenin forms adherent junction together with E-cadherin. Most of patients (87.5 %) with objective response had decreased membrane β-catenin expression, and that was statistically significant [34].…”

“…In his meta-analysis, Peng et al found that cut off ≥ 10 % was used in most of the published studies [27][28][29][30][31][32][33][34].…”