Activation of sonic hedgehog signaling pathway is an independent potential prognosis predictor in human hepatocellular carcinoma patients

作     者：Li Che Yan-Hua Yuan Jun Jia Jun Ren 

作者机构：Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Department of Medical OncologyPeking University Cancer Hospital & Institute 

出 版 物：《Chinese Journal of Cancer Research》 (中国癌症研究（英文版）)

年 卷 期：2012年第24卷第4期

页      面：323-331页

核心收录：

学科分类：1002[医学-临床医学] 100214[医学-肿瘤学] 10[医学] 

基　　金：supported by the Project 2009CB521700 of the National Basic Research Program of China ("973"Program) the Capital Development Grant (2007-2053) 

主　　题：Hepatocellular carcinoma hedgehog GLII sonic hedgehog patched smoothened prognosis 

摘      要：Objective： The activation of hedgehog （HH） pathway is implicated in the development of human malignancies including hepatocellular carcinoma （HCC）. However, the clinical impact of HH activation in HCC patients is still unclear. This study was conducted to confirm whether the expression of HH pathway components was associated with HCC progression and clinical outcome. Methods： This study was a sample-expanded and prolonged follow up of one of our previous studies. It included 46 HCC patients who underwent surgical treatment from 2002 to 2005. The expression of sonic HH （SHIq）, patched-1 （PTCHI）, smoothened （SMOH） and glioma-associated oncogene-1 （GLI1） genes in tumor and adjacent normal tissues extracted from the patients were examined by reverse transcription- polymerase chain reaction （RT-PCR） to explore the relationship between these genes and the clinical prognosis of HCC. Results： The expression levels ofSHH, PTCH1, SMOH and GLI1 in HCC tissues were 60.87%, 50.00%, 32.61% and 54.35%, respectively. The expression levels of SHH-related molecules were relatively intense in cancer tissue, but insignificantly correlated with any clinicopathological factors of tumor. Transcriptional factor GLI1 was the only molecule associated with poor prognosis among the HCC patients. The expression of GLI1 gene in tumor tissues was significantly related with disease-free survival （DFS） （P=0.042） and overall survival （OS） （P=0.030）. The simultaneous expression of GLI1 in tumor and adjacent normal liver tissues correlated with DFS （P〈0.029） and OS （P〈0.025）. Conclusions： HH signaling activation is an important event in the development of human HCC. The expression of GLI1 in SHH pathway is possibly involved in HCC progression, which may be a useful prognostic indicator of HCC.