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浙江大学学报(医学版)  2014, Vol. 43 Issue (4): 397-405    DOI: 10.3785/j.issn.1008-9292.2014.06.005
专题报道     
分泌型卷曲相关蛋白1、β联蛋白、上皮钙黏着蛋白在结直肠癌中的表达及意义
欧玉荣1,刘娟1,高杉2,景桂英1,承泽农1,董修琴1
1. 蚌埠医学院第一附属医院病理科 蚌埠医学院病理学教研室,安徽 蚌埠233004 2. 安徽医科大学药理学教研室,安徽 合肥 230032
Expression of secreted frizzled related protein 1,β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances
OU Yu-rong1, LIU Juan1, GAO Shan2, JING Gui-ying1, CHENG Ze-nong1, DONG Xiu-qin1
1. Department of Pathology, First Affiliated Hospital of Bengbu Medical College, Bengbu 233004, China; 2. Department of Pharmacology, College of Basic Medical, Anhui Medical University, Hefei 230032, China
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摘要: 目的: 探讨Wnt信号通路抑制因子分泌型卷曲相关蛋白1(SFRP1)在结直肠癌组织中的表达,及其与β联蛋白(β-catenin)和上皮钙黏着蛋白(E-cadherin)蛋白表达的关系,并探讨其临床意义。 方法:应用逆转录PCR检测60份结直肠癌及其癌旁正常黏膜中SFRP1、β-catenin和E-cadherin基因mRNA表达水平;同时应用免疫组织化学染色法(Elivision法)检测相同组织中SFRP1、β-catenin和E-cadherin蛋白的表达,并探讨其相关性及与临床病理因素的关系。 结果:60份组织中,52份结直肠癌组织及其癌旁正常黏膜中RNA提取成功;SFRP1 mRNA相对表达量分别为0.4837±0.1532和0.7170±0.1830;β-catenin mRNA相对表达量分别为0.9293±0.3705和0.6469±0.3166;E-cadherin mRNA相对表达量分别为0.5556±0.2535和0.9422±0.2372,两组比较差异均有统计学意义(均P<0.01);SFRP1 mRNA表达与肿瘤淋巴结转移有关(P<0.05)。SFRP1蛋白在结直肠癌中的阳性表达率为31.67%(19/60),显著低于癌旁正常结直肠黏膜组织75.00%(45/60)的阳性表达率;SFRP1 蛋白表达与临床病理各因素无关。β-catenin、E-cadherin在结直肠癌中的异常表达率分别为75.00%(45/60)、58.33%(35/60),显著高于癌旁正常结直肠黏膜组织1.67%(1/60)、6.67%(4/60)的异常表达率;β-catenin和E-cadherin异常表达与肿瘤的分化程度、淋巴结转移和Dukes分类有关。结直肠癌中SFRP1蛋白的表达与β-catenin和E-cadherin的异常表达呈负相关(r=-0.517,r=-0.442, 均P<0.01)。 结论:结直肠癌中SFRP1的表达下调导致Wnt信号通路出现异常活化,并引起β-catenin和E-cadherin异常表达增加。提示SFRP1失活及水平下调是结直肠癌启动及促进的重要因素。
Abstract:Objective: To investigate the expression of secreted frizzled-related protein 1 (SFRP1), β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significance. Methods: The expression of SFRP1, β-catenin and E-cadherin mRNA and protein in tumor and pericancerous tissue samples from 60 cases of colorectal cancer was assayed by reverse-transcription PCR and immunohistochemistry, respectively. The correlation of their expression with clinicopathological factors of colorectal cancer was analyzed. Results: In 52/60 cases the relative mRNA expression of SFRP1 in cancer tissue and pericancerous tissue was 0.4837 ± 0.1532 and 0.7170 ± 0.1830; for β-catenin was 0.9293 ± 0.3705 and 0.6469±0.3166; and for E-cadherin was 0.5556±0.2535 and 0.9422±0.2372 (P<0.01), respectively. SFRP1 mRNA expression was associated with lymphatic metastasis (P<0.05). The positive rate of SFRP1 in colorectal cancer was 31.67% (19/60), and was significantly lower than that in pericancerous colorectal mucosa (75.00%, 45/60). No relationship between SFRP1 protein expression and clinical pathology was found. Abnormal expression rates of β-catenin and E-cadherin in colorectal cancer were 75.00% (45/60) and 58.33% (35/60), respectively, which were significantly higher than that in pericancerous colorectal mucosa (1.67% and 6.67%), respectively. Abnormal β-catenin and E-cadherin expression was associated with tumor differentiation, lymphatic metastasis and Dukes staging. SFRP1 protein expression was negatively correlated with β-catenin and E-cadherin expression (r=-0.517,-0.442,Ps<0.01). Conclusion: Down-regulation of SFRP1 in colorectal cancer may cause abnormal Wnt signaling and induce abnormal β-catenin and E-cadherin expression, indicating that SFRP1 might be involved in the development and progression of colorectal cancer, and could be a novel therapeutic target for colorectal cancer.
收稿日期: 2014-01-10
基金资助:国家自然科学基金面上项目(81073088);安徽省教育厅自然科学研究项目(2010 KJ116B);蚌埠市科技局科研项目(200903020).
作者简介: 欧玉荣(1974-), 女, 副教授,硕士生导师,从事消化道肿瘤病理研究;E-mail: snowyc1220@163.com
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引用本文:

欧玉荣,等. 分泌型卷曲相关蛋白1、β联蛋白、上皮钙黏着蛋白在结直肠癌中的表达及意义[J]. 浙江大学学报(医学版), 2014, 43(4): 397-405.
OU Yu-rong,et al. Expression of secreted frizzled related protein 1,β-catenin and E-cadherin in colorectal carcinoma and its clinicopathological significances . Journal of ZheJiang University(Medical Science), 2014, 43(4): 397-405.

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http://www.zjujournals.com/xueshu/med/CN/10.3785/j.issn.1008-9292.2014.06.005      或      http://www.zjujournals.com/xueshu/med/CN/Y2014/V43/I4/397

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