胆管细胞癌中CtBP1、Zeb1、Zeb2与E-cadherin蛋白的表达及临床意义
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摘要
目的探讨转录抑制因子Zeb1、Zeb2、转录辅抑制因子CtBP1及其靶基因E-cadherin在胆管细胞癌中的表达及CtBP1、Ecadherin的临床意义。方法采用免疫组化法检测胆管细胞癌及癌旁组织芯片中CtBP1、Zeb1、Zeb2和E-cadherin的表达。结果CtBP1在胆管细胞癌及癌旁组织中的阳性率分别为44.44%和17.86%,Zeb2分别为34.92%和10.71%,E-cadherin分别为50.79%和100%,组间差异均有统计学意义(P均<0.05)。Zeb1在胆管细胞癌仅1例表达,而在癌旁组织中不表达。CtBP1与胆管细胞癌的分化程度相关(P<0.05),E-cadherin与胆管细胞癌的分化程度及远处转移有关(P均<0.05)。E-cadherin和CtBP1及Zeb2表达呈负相关(r=-0.034、-0.029,P均<0.001),CtBP1和Zeb2表达呈正相关(r=0.228,P=0.005)。结论胆管细胞癌中CtBP1、Zeb2与E-cadherin均表达异常,CtBP1、Zeb2可能共同参与E-cadherin表达调控。联合检测CtBP1和E-cadherin有望成为评估胆管细胞癌恶性生物学行为的参考指标。
Purpose To investigate the expression of transcriptional suppressor CtBP1,Zeb1,Zeb2 and their target gene E-cadherin, and their significance in cholangiocarcinoma.Methods The expression of CtBP1,Zeb1,Zeb2 and E-cadherin proteins in cholangiocarcinoma and the paired non-neoplastic tissue array were detected by the immunohistohemical staining. Results The positive rates of CtBP1 expression in cholangiocarcinoma and the paired non-neoplastic tissue were44. 44% and 17. 86%, these of Zeb2 were 34. 92% and10. 71%,and these of E-cadherin were 50. 79% and 100%,respectively. The differences between the groups were statistically significant(all P < 0. 05). There was only one case with expression of Zeb1 in cholangiocarcinoma,but no expression in the paired non-neoplastic tissue. CtBP1 was correlated with the degree of differentiation of cholangiocarcinoma(P < 0. 05). Ecadherin was related to the differentiation degree,and distant metastasis of cholangiocarcinoma(all P < 0. 05). The E-cadherin expression was negatively correlated with CtBP1 and Zeb2(r=-0. 034,-0. 029,all P < 0. 05). The Zeb2 expression was positively correlated with CtBP1(r = 0. 228,P = 0. 005). Conclusion CtBP1,Zeb2 and E-cadherin express abnormally in cholangiocarcinoma. CtBP1,Zeb2 may be involved in the regulation of E-cadherin expression. Joint detection of CtBP1 and Ecadherin is expected to be a reference index to evaluate the malignant biological behavior of cholangiocarcinoma.
Purpose To investigate the expression of transcriptional suppressor CtBP1,Zeb1,Zeb2 and their target gene E-cadherin, and their significance in cholangiocarcinoma.Methods The expression of CtBP1,Zeb1,Zeb2 and E-cadherin proteins in cholangiocarcinoma and the paired non-neoplastic tissue array were detected by the immunohistohemical staining. Results The positive rates of CtBP1 expression in cholangiocarcinoma and the paired non-neoplastic tissue were44. 44% and 17. 86%, these of Zeb2 were 34. 92% and10. 71%,and these of E-cadherin were 50. 79% and 100%,respectively. The differences between the groups were statistically significant(all P < 0. 05). There was only one case with expression of Zeb1 in cholangiocarcinoma,but no expression in the paired non-neoplastic tissue. CtBP1 was correlated with the degree of differentiation of cholangiocarcinoma(P < 0. 05). Ecadherin was related to the differentiation degree,and distant metastasis of cholangiocarcinoma(all P < 0. 05). The E-cadherin expression was negatively correlated with CtBP1 and Zeb2(r=-0. 034,-0. 029,all P < 0. 05). The Zeb2 expression was positively correlated with CtBP1(r = 0. 228,P = 0. 005). Conclusion CtBP1,Zeb2 and E-cadherin express abnormally in cholangiocarcinoma. CtBP1,Zeb2 may be involved in the regulation of E-cadherin expression. Joint detection of CtBP1 and Ecadherin is expected to be a reference index to evaluate the malignant biological behavior of cholangiocarcinoma.
引文
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[11]Vandewalle C,Van Roy F,Berx G.The role of the ZEB family of transcription factors in development and disease[J].Cell Mol Life Sci,2009,66(5):773-787.
[12]曾思恩,肖胜军,张小玲,陈秋月.肝细胞肝癌中转录辅抑制因子Ct BP1与其靶基因E-cadherin的表达[J].临床与实验病理学杂志,2010,26(6):655-657.
[2]Wong T S,Gao W,Chan J Y.Transcription regulation of E-cadherin by zinc finger E-box binding homeobox proteins in solid tumors[J].Biomed Res Int,2014,2014:921564.
[3]Sundqvist A,Sollerbrant K,Svensson C.The carboxy-terminal region of adenovirus E1A activates transcription through targeting of a C-terminal binding protein-histone deacetylase complex[J].FEBS Lett,1998,429(2):183-188.
[4]Lee J O,Kwun H J,Jung J K,et al.Hepatitis B virus X protein represses E-cadherin expression via activation of DNA methyltransferase 1[J].Oncogene,2005,24(44):6617-6625.
[5]肖胜军,张小玲,容明智,等.转录辅抑制因子Ct BP1与其靶基因E-cadherin在结肠腺癌中的表达[J].世界华人消化杂志,2009,17(36):3756-3759.
[6]Araki K,Shimura T,Suzuki H,et al.E/N-cadherin switch mediates cancer progression via TGF-β-induced epithelial-to-mesenchymal transition in extrahepatic cholangiocarcinoma[J].Br J Cancer,2011,105(12):1885-1893.
[7]Schmalhofer O,Brabletz S,Brabletz T.E-cadherin,beta-catenin,and ZEB1 in malignant progression of cancer[J].Cancer Metastasis Rev,2009,28(1-2):151-166.
[8]Peinado H,Olmeda D,Cano A.Snail,Zeb and b HLH factors in tumour progression:an alliance against the epithelial phenotype[J]?Nat Rev Cancer,2007,7(6):415-428.
[9]Postigo A A,Depp J L,Taylor J J,et al.Regulation of Smad signaling through a differential recruitment of coactivators and corepressors by ZEB proteins[J].EMBO J,2003,22(10):2453-2462.
[10]Pena C,Garcia J M,Garcia V,et al.The expression levels of the transcriptional regulators p300 and Ct BP modulate the correlations between SNAIL,ZEB1,E-cadherin and vitamin D receptor in human colon carcinomas[J].Int J Cancer,2006,119(9):2098-2104.
[11]Vandewalle C,Van Roy F,Berx G.The role of the ZEB family of transcription factors in development and disease[J].Cell Mol Life Sci,2009,66(5):773-787.
[12]曾思恩,肖胜军,张小玲,陈秋月.肝细胞肝癌中转录辅抑制因子Ct BP1与其靶基因E-cadherin的表达[J].临床与实验病理学杂志,2010,26(6):655-657.