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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

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ABSTRACT

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.

No MeSH data available.


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Expression of E-cadherin. (A) Absolute loss of E-cadherin expression in HCC tissues compared to strong and diffuse membranous staining in the adjacent normal liver parenchyme (star) (magnifiction, ×10). (B) Enlarged image of (A) (magnification, ×20). (C) Weakening of E-cadherin expression in HCC tissues. The adjacent bile duct is indicated by an arrow (magnification, ×10). (D) Enlarged image of (C) (magnification, ×20). HCC, hepatocellular carcinoma.
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f2-ol-0-0-4884: Expression of E-cadherin. (A) Absolute loss of E-cadherin expression in HCC tissues compared to strong and diffuse membranous staining in the adjacent normal liver parenchyme (star) (magnifiction, ×10). (B) Enlarged image of (A) (magnification, ×20). (C) Weakening of E-cadherin expression in HCC tissues. The adjacent bile duct is indicated by an arrow (magnification, ×10). (D) Enlarged image of (C) (magnification, ×20). HCC, hepatocellular carcinoma.

Mentions: Strong E-cadherin expression was identified in all NTL tissues (100%), whereas only 8 HCC tissues were positive for E-cadherin expression, which showed a statistically significant difference between the two groups (P<0.001) (Fig. 2). Twist expression was also significantly different between the two groups, with Twist expression identified in 8 NTL tissues (40.0%) and 34 HCC tissues (81.0%) (P=0.003; Table II; Fig. 3).


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
Expression of E-cadherin. (A) Absolute loss of E-cadherin expression in HCC tissues compared to strong and diffuse membranous staining in the adjacent normal liver parenchyme (star) (magnifiction, ×10). (B) Enlarged image of (A) (magnification, ×20). (C) Weakening of E-cadherin expression in HCC tissues. The adjacent bile duct is indicated by an arrow (magnification, ×10). (D) Enlarged image of (C) (magnification, ×20). HCC, hepatocellular carcinoma.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4998202&req=5

f2-ol-0-0-4884: Expression of E-cadherin. (A) Absolute loss of E-cadherin expression in HCC tissues compared to strong and diffuse membranous staining in the adjacent normal liver parenchyme (star) (magnifiction, ×10). (B) Enlarged image of (A) (magnification, ×20). (C) Weakening of E-cadherin expression in HCC tissues. The adjacent bile duct is indicated by an arrow (magnification, ×10). (D) Enlarged image of (C) (magnification, ×20). HCC, hepatocellular carcinoma.
Mentions: Strong E-cadherin expression was identified in all NTL tissues (100%), whereas only 8 HCC tissues were positive for E-cadherin expression, which showed a statistically significant difference between the two groups (P<0.001) (Fig. 2). Twist expression was also significantly different between the two groups, with Twist expression identified in 8 NTL tissues (40.0%) and 34 HCC tissues (81.0%) (P=0.003; Table II; Fig. 3).

View Article: PubMed Central - PubMed

ABSTRACT

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&lt;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.

No MeSH data available.


Related in: MedlinePlus