Activation of sonic hedgehog signaling pathway is an independent potential prognosis predictor in human hepatocellular carcinoma patients.
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 (SHH), patched-1 (PTCH1), 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 of SHH, 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.
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Department of Medical Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China.
Li
L
Che
Yan-Hua
YH
Yuan
Jun
J
Jia
Jun
J
Ren
GLI1; Hepatocellular carcinoma; hedgehog; patched; prognosis; smoothened; sonic hedgehog