Evaluation of glioma-associated oncogene 1 expression and its correlation with the expression of sonic hedgehog, E-cadherin and S100a4 in human hepatocellular carcinoma

The aim of the present study was to analyze the mRNA and protein expression of glioma-associated oncogene 1 (Gli1) in hepatocellular carcinoma (HCC) and its correlation with sonic hedgehog (Shh), one of the ligands of hedgehog (Hh) signaling, and two epithelial-mesenchymal transition (EMT) markers, E-cadherin and S100a4. We also investigated the potential crosstalk between Hh signaling and EMT in HCC. Paired HCC and normal tumor-adjacent tissues were freshly collected from 30 primary HCC patients. Gli1 expression at both the mRNA and protein level was examined by reverse transcription-polymerase chain reaction and immunohistochemistry. The protein expression of Shh, E-cadherin and S100a4 was evaluated by immunohistochemistry to identify correlations with Gli1. The mRNA and protein expression of Gli1 was significantly up-regulated in the HCC tumor tissues compared to the normal tumor-adjacent tissues (P<0.01, respectively). Gli1 protein expression in HCC was closely correlated with liver cirrhosis (r=0.460, P=0.011<0.05), intrahepatic metastases (r=0.399, P=0.029<0.05), portal vein invasion (r=0.367, P=0.046<0.05), high Edmonson-Steiner classification (r=0.391, P=0.032<0.05) and advanced TNM stage (r=0.416, P=0.022<0.05). In HCC tissues, Gli1 protein expression was positively correlated with Shh (r=0.584, P=0.001<0.05) and S100a4 (r=0.49, P=0.006<0.05), and negatively correlated with E-cadherin (r=-0.439, P=0.015<0.05). Gli1 was found to be up-regulated in HCC tissues and closely correlated with clinicopathological characteristics, indicating the enhanced metastatic potential of HCC. Furthermore, the increased expression of Gli1 in HCC cells may be attributed to Shh produced aberrantly by the cells themselves. Finally, Gli1 may play an important role in HCC invasion and metastasis by inducing EMT.