Significance of the hedgehog pathway-associated proteins Gli-1 and Gli-2 and the epithelial-mesenchymal transition-associated proteins Twist and E-cadherin in hepatocellular carcinoma.

It has been found that abnormal activation of the hedgehog (Hh) signaling pathway is involved in the occurrence, invasion and metastasis of malignant tumors. In addition, epithelial-mesenchymal transition (EMT) also performs an important function in the invasion and metastasis of malignant tumors. However, the significance of the Hh signaling pathway and EMT in hepatocellular carcinoma (HCC) remains unknown. In the present study, the expression of Gli family zinc finger 1 (Gli-1) and Gli family zinc finger 2 (Gli-2), which are key transcriptional factors in the Hh signaling pathway, and Twist and E-cadherin, which are two factors involved in EMT, was examined in 42 patients with HCC and 20 cases of non-tumorous liver (NTL) tissue by immunohistochemistry. Clinicopathological information was collected in order to analyze the correlation of the Hh signaling pathway with EMT. The present study aimed to examine the difference in the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL to assess the diagnostic value of these factors in HCC. Additionally, the present study aimed to elucidate the correlation between those proteins and other clinicopathological parameters. Whether abnormal activation of the Hh signaling pathway is closely associated with EMT was also evaluated. Gli-1 and Twist expression was found to be significantly increased and E-cadherin expression was found to be decreased in HCC in contrast to NTL (Gli-1, P=0.019; Twist, P=0.003; E-cadherin, P<0.001). Increased Twist expression was associated with the tumor size (P=0.043), and loss of or decreased E-cadherin expression was associated with the histological type of HCC (P=0.021). There was an inverse association between the expression of Twist and E-cadherin (P=0.006). These results showed that Twist overexpression by induction of EMT changes is involved in the occurrence and progression of HCC. However, the role of Hh signaling pathway-associated proteins in HCC may require elucidation by additional studies using additional materials in the future.