Ou Yurong, Jing Guiying, Liu Juan, Gao Shan, Cheng Zenong, Dong Xiuqin
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi. 2015 Aug;32(4):854-61.
Abnormal activation of Wnt signaling pathway is closely related to the occurrence of tumor, and T cell factor 4 (Tcf4 ) and beta-catenin are important signal transmission factors of this pathway. The aim of the present study is to explore the significance and correlation between expression of Tcf4, beta-catenin and secreted frizzled related protein 1(SFRP1), suppressor gene of Wnt signaling pathway, in colorectal carcinoma and their correlations to the clinicopathological factors. The expressions of Tcf4, beta-catenin and SFRP1 were performed with immunohistochemistry staining in 97 cases of primary colorectal carcinoma and 40 cases of normal colorectal mucosa tissues. The results showed that the abnormal expression rates of Tcf4 and beta-catenin in colorectal carcinoma were significantly higher than those in the control groups (P<0.01). The positive rate of SFRP1 was significantly lower than those in the control groups (P<0.01). The abnormal expression rates of Tcf4 and beta-catenin were also related to the lymph node metastasis and Dukes stage (P<0.05). A significant correlation was found between the expressions of SFRP1 and Tcf4, beta-catenin (P<0.05). Overexpression of Tcf4 and beta-catenin was related to poor prognosis (P<0.05). But the survival rates of the group with SFRP1 expressions were higher than those in group without SFRP1 expressions (P<0.05). Cox multifactor regression analysis indicated that Dukes stage, expression of beta-catenin and SFRP1 were independent risk factors of colorectal carcinoma (P<0.05). The results suggested that the abnormal expression of Tcf4 and beta-catenin in colorectal cancer may be related to the reduced or absent expression of SFRP1. beta-catenin accumulation in the nuclei formed complexes with Tcf4 is one of the important molecular switch maintaining colorectal malignant phenotype. The combined detection of these indexes may perform an important role in predicting the progression and prognosis of colorectal cancer, and could provide new molecular targets for gene treatment of colorectal cancer.
Wnt信号通路的异常激活与肿瘤的发生密切相关，而T细胞因子4（Tcf4）和β-连环蛋白是该通路重要的信号传导因子。本研究旨在探讨Tcf4、β-连环蛋白及Wnt信号通路抑制基因分泌型卷曲相关蛋白1（SFRP1）在结直肠癌中的表达意义及其相互关系，以及它们与临床病理因素的相关性。采用免疫组织化学染色法检测97例原发性结直肠癌组织及40例正常结直肠黏膜组织中Tcf4、β-连环蛋白和SFRP1的表达。结果显示，结直肠癌中Tcf4和β-连环蛋白的异常表达率显著高于对照组（P<0.01）。SFRP1的阳性率显著低于对照组（P<0.01）。Tcf4和β-连环蛋白的异常表达率还与淋巴结转移及Dukes分期有关（P<0.05）。SFRP1与Tcf4、β-连环蛋白的表达之间存在显著相关性（P<0.05）。Tcf4和β-连环蛋白的过表达与预后不良有关（P<0.05）。但SFRP1表达组的生存率高于无SFRP1表达组（P<0.05）。Cox多因素回归分析表明，Dukes分期、β-连环蛋白和SFRP1的表达是结直肠癌的独立危险因素（P<0.05）。结果提示，结直肠癌中Tcf4和β-连环蛋白的异常表达可能与SFRP1表达降低或缺失有关。β-连环蛋白在细胞核内积聚并与Tcf4形成复合物是维持结直肠恶性表型的重要分子开关之一。联合检测这些指标可能对预测结直肠癌的进展和预后具有重要作用，并可为结直肠癌的基因治疗提供新的分子靶点。
