간세포암종에서 Hedgehog 경로관련단백 (Gli-1, Gli-2)과 상피간엽전환조절단백 (Twist, E-cadherin)발현의 의의

Abstract

Abnormal activation of the hedgehog (Hh) signaling pathway has been found to be involved in the occurrence, invasion, and metastasis of cancers. Epithelial-mesenchymal transition (EMT) also plays an important role in the invasion and metastasis of cancers. However, the significance of the Hh signaling pathway and EMT in the hepatocellular carcinoma (HCC) is still unclear. In the present study, the expression of Gli-1 and Gli-2 (key transcriptional factor in the Hh signaling pathway), and Twist and E-cadherin (two factors involved in EMT) were examined in 42 patients with HCC and 20 cases of Nontumorous Liver tissue (NTL) by immunohistochemistry, and clinicopatholgical information were collected in order to analyze the correlation of Hh signaling pathway with EMT. This study was aimed to investigate the difference of the expression of Gli-1, Gli-2, E-cadherin and Twist in HCC and NTL for the diagnostic value of HCC. Moreover, aimed to elucidate the correlation between those proteins and other clinicopathologic parameters. Whether abnormal activation of the Hh signaling pathway is closely related to the EMT was also evaluated. Gli-1 and Twist expression was significantly increased, and E-cadherin expression was decreased in HCC in contrast to NTL (p=0.019, p=0.003, p=<0.001, respectively). The increased Twist expression was correlated with tumor size (p=0.043), and deceased E-cadherin expression was correlated with histologic type of HCC (p=0.021). There was inverse correlation between 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-related protein in HCC will be needed to determine by additional research using more materials in future.