摘要
Wnt信号通路的异常激活与肿瘤的发生密切相关,T细胞因子4(Tcf4)和β连环蛋白(β-catenin)是该通路中重要的信号传递因子。本文应用免疫组织化学染色检测97例结直肠癌组织和40例正常黏膜组织中Tcf4、β-catenin和Wnt信号通路抑制因子分泌型卷曲相关蛋白1(SFRP1)的表达关系,探讨其临床意义及与预后的关系。结果显示:在结直肠癌中,Tcf4及β-catenin异位表达显著高于正常黏膜组织(P<0.01),SFRP1表达显著低于正常黏膜组织(P<0.01);结直肠癌中SFRP1的表达与Tcf4和β-catenin异位表达呈负相关(r=-0.599,P<0.01;r=-0.250,P<0.05);Tcf4和β-catenin异位表达均与淋巴结转移和Dukes分期有关(P<0.05),SFRP1表达与与肿瘤浸润深度有关(P<0.05);Kaplan-Meier生存分析表明,Tcf4和β-catenin异位表达的患者生存率明显低于阴性者(P<0.01),而SFRP1阳性表达的患者生存率明显高于阴性者(P<0.01);多因素分析表明β-catenin异位表达和SFRP1的表达及Dukes分期是影响结直肠癌患者预后的独立因素(P<0.05)。结果提示在结直肠癌中Wnt信号通路因子Tcf4和β-catenin异位表达,可能与SFRP1的表达下调或缺失有关;β-catenin在细胞核内积聚与Tcf4形成复合体是维持结直肠癌恶性表型的重要分子开关;三者联合检测可能对结直肠癌的进展及预后判断有着重要意义,并为结直肠癌的基因治疗提供新的分子靶点。
Abnormal activation of Wnt signaling pathway is closely related to the occurrence of tumor, and T cell factor 4 （Tcf4） and β-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, β-catenin and secreted frizzled related protein I（SFRP1）, suppressor gene of Wnt signaling pathway, in colorectal carcinoma and their correlations to the clinico- pathological factors. The expressions of Tcf4, β-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 β-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 β-catenin were also related to the lymph node metas tasis and Dukes stage （P〈0.05）. A significant correlation was found between the expressions of SFRP1 and Tcf4, β-catenin （P〈0.05）. Over-expression of Tef4 and β-eatenin 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 β-catenin and SFRP1 were inde- pendent risk factors of colorectal carcinoma （P〈0.05）. The results suggested that the abnormal expression of Tcf4 and β-eatenin in colorectal cancer may be related to the reduced or absent expression of SFRP1. β-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.
出处
《生物医学工程学杂志》
EI
CAS
CSCD
北大核心
2015年第4期854-861,共8页
Journal of Biomedical Engineering
基金
国家自然科学基金资助项目(81073088)
安徽省教育厅自然科学研究资助项目(2010KJ116B)
蚌埠市科技局科研资助项目(200903020)
