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Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients.

Huang XY, Zhang C, Cai JB, Shi GM, Ke AW, Dong ZR, Zhang PF, Fan J, Peng BG, Zhou J - PLoS ONE (2014)

Bottom Line: Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss.Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.

View Article: PubMed Central - PubMed

Affiliation: The Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China; Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, PR China.

ABSTRACT

Background: The aim of this study is to investigate the expression profile of multiple epithelial mesenchymal transition (EMT)-related molecules in intrahepatic cholangiocarcinoma (ICC) and the related prognostic significance.

Methods: Immunohistochemistry was performed to determine the expression of E-cadherin, Vimentin, Snail, slug and β-catenin in a tissue microarray consisting of tumor tissues of 140 ICC patients undergoing curative resection. The correlation between the expression of these molecules and the clinicopathological characteristics of ICC patients was analyzed, and their prognostic implication was evaluated.

Results: Reduced E-cadherin and increased Vimentin expression, the characteristic changes of EMT, identified in 55.0% and 55.7% of primary ICCs, respectively, were correlated with lymphatic metastasis and poorer overall survival (OS) and disease-free survival (DFS) of ICCs. The overexpression of snail and nonmembranous β-catenin, which are the major regulators of the EMT, were identified in 49.2% and 45.7% of primary ICCs, while little slug expression was detected in ICCs. Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss. The overexpression of snail predicted worse OS and DFS. Snail overexpression correlated with the down-regulation of E-cadherin and the up-regulation of Vimentin. Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.

Conclusions: These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.

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Related in: MedlinePlus

Immunohistochemical analysis of E-cadherin and Vimentin in ICC tissues.(A, B) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative E-cadherin expression. (C, D) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative Vimentin expression.
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pone-0096860-g001: Immunohistochemical analysis of E-cadherin and Vimentin in ICC tissues.(A, B) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative E-cadherin expression. (C, D) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative Vimentin expression.

Mentions: In adjacent nontumorous liver tissues, Interlobular bile ducts showed strong and homogeneous membranous staining (Figure S1). In the tumors, three types of distinct staining patterns were observed (strong vs. weak and absent, Figure S1). We observed lymphatic metastasis more frequently in tumors expressing either weak or absent E-cadherin than in tumors in which E-cadherin expression was strong (P<0.05; Table S1). The 2-year and 5-year OS rates in the positive E-cadherin group were significantly higher than the rates in the negative E-cadherin group (49.2% vs. 22.1% and 24.9% vs. 17.5%, respectively; Figure 1A). For the DFS analyses, negative E-cadherin expression was significantly associated with higher recurrence (Figure 1B).


Comprehensive multiple molecular profile of epithelial mesenchymal transition in intrahepatic cholangiocarcinoma patients.

Huang XY, Zhang C, Cai JB, Shi GM, Ke AW, Dong ZR, Zhang PF, Fan J, Peng BG, Zhou J - PLoS ONE (2014)

Immunohistochemical analysis of E-cadherin and Vimentin in ICC tissues.(A, B) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative E-cadherin expression. (C, D) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative Vimentin expression.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4016113&req=5

pone-0096860-g001: Immunohistochemical analysis of E-cadherin and Vimentin in ICC tissues.(A, B) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative E-cadherin expression. (C, D) Kaplan-Meier survival analysis of OS and DFS in ICC cases with positive versus negative Vimentin expression.
Mentions: In adjacent nontumorous liver tissues, Interlobular bile ducts showed strong and homogeneous membranous staining (Figure S1). In the tumors, three types of distinct staining patterns were observed (strong vs. weak and absent, Figure S1). We observed lymphatic metastasis more frequently in tumors expressing either weak or absent E-cadherin than in tumors in which E-cadherin expression was strong (P<0.05; Table S1). The 2-year and 5-year OS rates in the positive E-cadherin group were significantly higher than the rates in the negative E-cadherin group (49.2% vs. 22.1% and 24.9% vs. 17.5%, respectively; Figure 1A). For the DFS analyses, negative E-cadherin expression was significantly associated with higher recurrence (Figure 1B).

Bottom Line: Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss.Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.

View Article: PubMed Central - PubMed

Affiliation: The Department of Hepatobiliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China; Liver Cancer Institute, Zhongshan Hospital, Fudan University, Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, PR China.

ABSTRACT

Background: The aim of this study is to investigate the expression profile of multiple epithelial mesenchymal transition (EMT)-related molecules in intrahepatic cholangiocarcinoma (ICC) and the related prognostic significance.

Methods: Immunohistochemistry was performed to determine the expression of E-cadherin, Vimentin, Snail, slug and β-catenin in a tissue microarray consisting of tumor tissues of 140 ICC patients undergoing curative resection. The correlation between the expression of these molecules and the clinicopathological characteristics of ICC patients was analyzed, and their prognostic implication was evaluated.

Results: Reduced E-cadherin and increased Vimentin expression, the characteristic changes of EMT, identified in 55.0% and 55.7% of primary ICCs, respectively, were correlated with lymphatic metastasis and poorer overall survival (OS) and disease-free survival (DFS) of ICCs. The overexpression of snail and nonmembranous β-catenin, which are the major regulators of the EMT, were identified in 49.2% and 45.7% of primary ICCs, while little slug expression was detected in ICCs. Cytoplasmic/nuclear β-catenin did not significantly predict worse DFS and was not related with E-cadherin loss. The overexpression of snail predicted worse OS and DFS. Snail overexpression correlated with the down-regulation of E-cadherin and the up-regulation of Vimentin. Inhibition of snail in an ICC cell line decreased the expression of E-cadherin, enhanced the expression of Vimentin and impaired the invasion and migration ability of ICC cells.

Conclusions: These data support the hypothesis that EMT plays vital roles in ICC progression and suggest that snail but not slug and β-catenin plays a crucial role in the EMT induction of ICC.

Show MeSH
Related in: MedlinePlus