Sonic Hedgehog信号传导通路基因在肝癌中的表达

Expression of genes related to Sonic Hedgehog signaling in human hepatocellular carcinomas

目的:研究Sonic Hedgehog(SHH)信号传导通路基因在肝癌中的表达,明确这些基因表达与临床预后的关系。方法:用逆转录聚合酶链反应法(reverse transcription-polymerase chain reaction chain reaction,RT-PCR)检测29例肝细胞癌肿瘤组织以及相对应的远癌正常组织中4种SHH基因的表达,同时用免疫组织化学二步法检测Shh和Ptch蛋白的表达。结果:所检测的4种SHH基因(Shh,Ptch,Smoh和Gli-1)在远癌正常肝癌组织中均低表达或无表达。在肝细胞癌组织中的表达率分别为51、68、48和62,而Shh和Ptch的蛋白和mRNA的表达量在癌组织中均显著相关(P=0.041和P=0.035)。Gli-1mRNA在远癌正常组织中的表达与预后明显相关,表达阳性者的无病生存时间(DFS)及总生存时间(OS)均明显缩短(P<0.05)。同时,Gli-1mRNA在肝癌组织及远癌正常组织中的表达均为阳性者的预后极差。结论:SHH信号传导通路在肝细胞癌中处于激活状态,SHH通路的激活可能是肝癌发生发展的重要因素,同时SHH传导通路基因标记物也有助于判断患者的预后。

Objective： To investigate the expression status of Sonic Hedgehog signaling genes and molecules in human hepatocellular carcinomas （HCC）, and to explore the relationship between these genes and clinical prognosis. Methods： HCC tissue and adjacent normal tissue from 29 HCC patients were assayed for the expression of hedgehog signaling genes by reverse transcription-polymerase chain reaction chain reaction （RT-PCR） techniques and for the expression of hedgehog signaling molecules by immunohistochemistry. The expressions of Shh,Ptch, Smoh, Gli-1 mRNA were assayed as well as Shh, Ptch proteins in 29 cases of HCC and in 29 liver tissues adjacent to the tumor. Results： Expression of Shh mRNA was detectable in about 51% of HCCs examined. Consistent with this, hedgehog target genes Ptch, Smoh and Gli-1 mRNA were expressed in over 68%, 48% and 62% of the tumors, respectively, and the expressions of Shh and Ptch proteins in HCC tumor tissues correlated with those of Shh and Ptch mRNA in tumor tissues （P = 0. 041 and P =0. 035 ）. This suggested that the hedgehog pathway was frequently activated in HCCs. The simultaneous expression of Gli-1 in HCC and liver tissues adjacent to the tumor had significantly relationship with poor prognosis. Conclusion： Hedgehog signaling activation is an important event for development of human HCCs. It also suggests that markers for hedgehog signaling activation may be useful for the determination of prognosis.