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口腔鳞状细胞癌中β-连环蛋白的异常表达及其与ΔNp63、Notch-1 和临床病理因素的关系。

Aberrant expression of β-catenin and its association with ΔNp63, Notch-1, and clinicopathological factors in oral squamous cell carcinoma.

机构信息

Unit of Biochemistry, Department of Zoology, University of Madras, Guindy Campus, Chennai, Tamil Nadu, India.

出版信息

Clin Oral Investig. 2012 Aug;16(4):1275-88. doi: 10.1007/s00784-011-0605-0. Epub 2011 Sep 1.

Abstract

The present study focuses on the correlation between the expression pattern of β-catenin (component of Wnt signaling), ΔNp63 (proliferation marker), and Notch 1 (transmembrane receptor) in oral squamous cell carcinoma. The study also aims to investigate the interaction between β-catenin and ΔNp63 in oral cancer. Furthermore, we also analyzed the prognostic significance of β-catenin, ΔNp63, and Notch 1 in oral squamous cell carcinoma. Immunohistochemical analysis of β-catenin, ΔNp63, and Notch 1 were done in 62 cases of oral squamous cell carcinoma. Co-immunoprecipitation analysis was done to study the possible interaction between β-catenin and ΔNp63 in oral cancer. Kaplan-Meier method was used to estimate overall and disease-free survival, and the Log-rank test was used to compare the resulting curves. Statistically significant positive correlation was found between the localization of β-catenin and the expression of ΔNp63 (p = 0.001**, r (s) = 0.427), whereas, no significant association was found between the expression pattern of β-catenin and Notch 1. Interestingly, interaction between β-catenin and ΔNp63 was observed in oral carcinoma. Moreover, β-catenin and ΔNp63 may be related to worst survival in oral carcinoma. Statistically significant positive association between localization of β-catenin and expression of ΔNp63 suggests that they might have dependent roles in maintaining the proliferation of oral carcinoma cells. In addition, the downregulated expression of Notch 1 was related to invasion and differentiation status of oral carcinoma cells. Furthermore, β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma. On the other hand, interaction of β-catenin with ΔNp63 may be a key event in maintaining the proliferation of oral carcinoma cells. The present study indicates that β-catenin and ΔNp63 may be used as independent prognostic markers of oral carcinoma and the interaction of β-catenin with ΔNp63 may be a crucial event in regulating proliferation and differentiation of oral carcinoma cells, which may be used as a target for therapeutic implications.

摘要

本研究旨在探讨β-连环蛋白(Wnt 信号通路的组成部分)、ΔNp63(增殖标志物)和 Notch 1(跨膜受体)在口腔鳞状细胞癌中的表达模式之间的相关性。本研究还旨在研究β-连环蛋白在口腔癌中的相互作用。此外,我们还分析了β-连环蛋白、ΔNp63 和 Notch 1 在口腔鳞状细胞癌中的预后意义。对 62 例口腔鳞状细胞癌进行了β-连环蛋白、ΔNp63 和 Notch 1 的免疫组织化学分析。通过共免疫沉淀分析研究了口腔癌中β-连环蛋白和 ΔNp63 之间可能的相互作用。Kaplan-Meier 法用于估计总生存率和无病生存率,对数秩检验用于比较所得曲线。β-连环蛋白的定位与 ΔNp63 的表达呈统计学显著正相关(p = 0.001**,r(s)= 0.427),而β-连环蛋白的表达模式与 Notch 1 之间无显著相关性。有趣的是,在口腔癌中观察到β-连环蛋白和 ΔNp63 之间的相互作用。此外,β-连环蛋白和 ΔNp63 可能与口腔癌的最差生存有关。β-连环蛋白的定位与 ΔNp63 的表达呈统计学显著正相关,这表明它们在维持口腔癌细胞增殖方面可能具有依赖性作用。此外,Notch 1 的下调表达与口腔癌细胞的侵袭和分化状态有关。此外,β-连环蛋白和 ΔNp63 可用作口腔癌的独立预后标志物。另一方面,β-连环蛋白与 ΔNp63 的相互作用可能是维持口腔癌细胞增殖的关键事件。本研究表明,β-连环蛋白和 ΔNp63 可用作口腔癌的独立预后标志物,β-连环蛋白与 ΔNp63 的相互作用可能是调节口腔癌细胞增殖和分化的关键事件,可作为治疗意义的靶点。

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