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Wnt/β-连环蛋白信号通路作为晚期卵巢癌患者潜在的预后和预测标志物

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

作者信息

Bodnar Lubomir, Stanczak Aleksandra, Cierniak Szczepan, Smoter Marta, Cichowicz Marzena, Kozlowski Wojciech, Szczylik Cezary, Wieczorek Maciej, Lamparska-Przybysz Monika

机构信息

Department of Oncology, Military Institute of Medicine in Warsaw, 128 Szaserów Street, 04-141 Warsaw, Poland.

出版信息

J Ovarian Res. 2014 Feb 6;7:16. doi: 10.1186/1757-2215-7-16.

DOI:10.1186/1757-2215-7-16
PMID:24499657
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3926861/
Abstract

BACKGROUND

β-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).

METHODS

The 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.

RESULTS

In 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).

CONCLUSIONS

These findings support that WNT/β-catenin pathway and E-cadherin are important factors in advanced epithelial ovarian cancer.

摘要

背景

β-连环蛋白是WNT信号通路中的关键蛋白,它与E-钙黏蛋白共同形成黏附连接。在卵巢癌中,观察到β-连环蛋白、E-钙黏蛋白和WNT-1的异常表达,但其预后和预测作用尚不清楚。本研究的目的是阐明E-钙黏蛋白、β-连环蛋白和WNT-1在晚期上皮性卵巢癌(AEOC)中的预后和预测作用。

方法

通过免疫组织化学法检测AEOC中E-钙黏蛋白、β-连环蛋白和WNT-1的表达。评估这些蛋白表达与无进展生存期(PFS)和总生存期(OS)之间的相关性。统计分析包括Kaplan-Meier估计、对数秩检验、Spearman相关性分析和Cox比例风险模型。

结果

在卵巢癌中,发现E-钙黏蛋白、β-连环蛋白和WNT-1有强烈表达。多因素分析中,β-连环蛋白强膜表达是PFS的独立不良预测因素(HR 2.19,95%CI 1.09-4.39;p = 0.028),而单因素分析中,β-连环蛋白强膜表达是AOC患者OS的预后因素(p = 0.039)。多因素分析中,仅对一线化疗的耐药性是OS的不良独立预后因素(HR 16.84;95%CI 5.07-55.98;p < 0.0001)。此外,β-连环蛋白强膜表达与铂类化疗耐药相关(p = 0.027)。

结论

这些发现支持WNT/β-连环蛋白通路和E-钙黏蛋白是晚期上皮性卵巢癌的重要因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/908d/3926861/dc57a6254fd3/1757-2215-7-16-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/908d/3926861/c5aee79c34fa/1757-2215-7-16-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/908d/3926861/dc57a6254fd3/1757-2215-7-16-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/908d/3926861/c5aee79c34fa/1757-2215-7-16-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/908d/3926861/dc57a6254fd3/1757-2215-7-16-2.jpg

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