胶质瘤相关癌基因1在肝细胞癌中的表达及其与Shh、Vimentin、E-cad-herin蛋白的相关性研究

Gli1 expression and its relationship with the expression of Shh,Vimentin and E-cadherin in human hepatocellular carcinoma

目的:研究胶质瘤相关癌基因1(Gli1)在肝癌中的表达及其与肝癌临床病理特征之间的关系,探讨Gli1表达与sonic hedgehog通路配体Shh、EMT标记物Vimentin以及E-cadherin表达的相关性,由此分析其在肝癌EMT过程中的作用。方法:收集63例肝细胞癌组织及相对应的癌旁组织应用免疫组化,RT-PCR法检测Gli1在肝细胞癌及癌旁组织中的表达情况,同时应用免疫组化法检测Hedgehog信号通路配体Shh、EMT标记物Vimentin以及E-cadherin在肝细胞癌及癌旁组织中的表达情况,使用Mann-Whitney U检验分析肝细胞癌组织与癌旁正常组织Gli1的mRNA含量以及蛋白表达差异。使用卡方检验分析Gli1蛋白在肝细胞癌组织中的表达与患者临床特征的关系。使用Spearmen秩检验分析肝细胞癌组织中Gli1蛋白表达分别与Shh、Vimentin及E-cadherin这三种蛋白表达的关系。结果:肝细胞癌组织中Gli1蛋白及mRNA含量明显高于癌旁正常肝组织;Gli1蛋白表达分别与肿瘤肝内转移或淋巴结转移(χ2=6.205,P<0.05)、门静脉侵袭(χ2=4.014,P<0.05)、高Edmonson病理分级(χ2=19.668,P<0.05)以及TNM肿瘤分期较晚(χ2=7.091,P<0.05)有关;肝细胞癌组织中Gli1蛋白表达与Shh(r=0.574,P<0.05)、Vimentin蛋白(r=0.467,P<0.05)表达呈明显正相关,而与E-cadherin蛋白(r=-0.439,P<0.05)呈负相关。结论:Gli1在肝细胞癌中表达增加,且与肝癌侵袭转移有关的临床病理特征具有相关性,Gli1可能在Shh配体的作用下激活Hedgehog信号通路,并可能诱导肝癌发生与侵袭转移相关的EMT过程。

AIM： To investigate the expression and clin- ical features of glima-associated oncogene 1 （ Glil ） and its correlation with the expression of sonic hedgehog （Shh）, one of the ligands of hedgehog （Hh） signaling, and two epithelial-mesenchymal transition （EMT） markers, Vimentin and E-cadherin in human hepatocellular carcinoma（HCC）. METHODS： Paired HCC and normal tumor-adjacent tissues were collected from 63 HCC patients. Glil expression at both the protein and mRNA level were examined by immunohistochemistry and RT-PCR. The protein expression of Shh, Vimentin and E-cadherin were evaluated by immu- nohistochemistry to identify correlations with Glil. RE- SULTS： The protein and mRNA expression of Glil were sig- nificantly up-regulated in the HCC tumor tissues compared to the normal tumor-adjacent tissues. Glil protein expres- sion in HCC was closely correlated with intrahepatic metas- tases （X^2 = 6. 205, P 〈 0.05）, portal vein invasion （X^2 = 4.014, P 〈 0.05 ）, high Edmonson-Steiner classification （X^2 = 19.668, P 〈 0.05） and advanced TNM stage （X^2= 7.091, P 〈 0.05）. Glil protein expression was positively correlated with Shh （ r = 0.574, P 〈 0.05） and Vimentin （ r = 0.467, P 〈 0.05 ）, and negatively correlated with E-cadherin （ r= -0.439, P〈0.05）. CONCLUSION： Glil is up-regulated in HCCtissues and closely correlated with clinicopathological char- acteristics, the increased expression of Glil in HCC tissues may be attributed to Shh, and Glil may play an important role in HCC progression and metastasis by inducing EMT.