Sonic Hedgehog信号通路在肝细胞癌中的表达及意义

Expression of the Sonic Hedgehog signaling pathway in hepatocellular carcinoma and its significance

背景与目的:有研究表明Sonic Hedgehog(SHH)信号通路参与多种肿瘤的发生和发展,本研究通过检测SHH信号通路中蛋白Shh、Gli2在肝细胞癌(hepatocellular carcinoma,HCC)中的表达情况,探讨其与HCC各临床病理特征的关系和意义。方法:采用免疫组织化学法检测30例肝癌组织及10例正常肝组织中蛋白Shh、Gli2的表达;RT-PCR法检测10例HCC组织及相应癌旁组织中和肝癌细胞系HepG2、Huh7中Shh和Gli2mRNA的表达。结果:免疫组织化学法检测结果显示Shh、Gli2在HCC组织中阳性率分别为63.3%(19/30)和66.7%(20/30);Gli2的表达与HCC病理分级和肝门静脉侵犯相关(P=0.017,P=0.024)。Shh、Gli2在正常肝组织中无表达。RT-PCR检测结果显示HCC组织和HepG2、Huh7细胞系中都存在Shh、Gli2mRNA的表达。HCC组织中Shh、Gli2基因表达高于癌旁组织(P<0.05);Shh、Gli2 mRNA在Huh7中的表达强度高于HepG2,但两者间差异无统计学意义(P>0.05)。结论:Shh和Gli2在HCC细胞系和组织中的高表达,可能参与了肝癌的发生和发展,为肝癌的防治研究提供了新的实验依据。

Background and purpose：.It was reported that Sonic Hedgehog （SHH） signaling pathway was involved in carcinogenesis and progression of various tumor types. This study was designed to observe the expression of Shh and Gli2 in SHH signaling pathway in hepatocellular carcinoma （HCC） and to study the relationship between the expression of Shh and Gli2 and different clinicopathlogical characteristics, and further to explore the clinical significance. Methods：We studied 30 HCC tissues and 10 normal liver tissue slices using immunochemistry for the expression of Shh and Gli2, 10 fresh HCC tissues, adjacent-tumor tissues and 2 HCC cell lines HepG2, Huh7 by using RT-PCR for the mRNA expression of Shh and Gli2. Results：Immunochemistry showed in 30 HCC tissue slices, the positive ratios of the components of SHH signaling pathway Shh, Gli2 were 63.3% （19/30） and 66.7% （20/30）, respectively. Expression of Gli2 was significantly correlated with the pathological grade and the tumor invasion in hepatic portal vein （P=0.017 and P=0.024）. Shh and Gli2 did not express in normal liver tissue. RT-PCR showed Shh and Gli2 were detected as positive in both HCC tissues and lines. The expressions of Shh mRNA and Gli2 mRNA were higher in HCC than in adjacent-tumor tissues （P〈0.05）. The expressions of Shh mRNA and Gli2 mRNA were higher in Huh7 than in HepG2 cell lines, but no significant difference was found between them （P〉0.05）. Conclusion：The expressions of Shh and Gli2 were elevated in HCC, which indicated that SHH signaling pathway may be involved in human HCC carcinogenesis. The study may be useful for treatment of HCC.