摘要
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.
出处
《细胞与分子免疫学杂志》
CAS
CSCD
北大核心
2012年第5期536-539,543,共5页
Chinese Journal of Cellular and Molecular Immunology
基金
国家自然科学基金(81072052/H161)
陕西省科技攻关项目(2010K01-128)