Dataset Information

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

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 ?-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 ?-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 ?-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 ?-catenin plays a crucial role in the EMT induction of ICC.

SUBMITTER: Huang XY

PROVIDER: S-EPMC4016113 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Huang Xiao-Yong XY Zhang Chi C Cai Jia-Bin JB Shi Guo-Ming GM Ke Ai-Wu AW Dong Zhao-Ru ZR Zhang Peng-Fei PF Fan Jia J Peng Bao-Gang BG Zhou Jian J

PloS one 20140509 5

<h4>Background</h4>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.<h4>Methods</h4>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 express ...[more]

PMID: 24816558

Similar Datasets

Project description:Periostin, a secreted matricellular protein, has been reported to induce epithelial-mesenchymal transition (EMT), which increases motility and invasiveness in various epithelial cancer cells. Periostin is also overexpressed in intrahepatic cholangiocarcinoma (ICC) and suggested to be a biomarker for tumor progression and poor prognosis; however, its functional role in ICC is not fully understood. Here, we investigated whether periostin influences malignant potential through the induction of EMT in ICC. Analyses of surgical resected ICC specimens revealed that the gene expression of periostin was significantly higher in ICC tumors than in adjacent nontumor liver tissues and was closely correlated with the expression of mesenchymal markers, including N-cadherin, vimentin, and fibronectin. However, the expression level of periostin varied in each case. Consistently, the expression of periostin in HuH28 (an undifferentiated ICC cell) was markedly higher than in HuCCT-1 (a moderately differentiated ICC cell). In addition, high-level secretion of periostin into culture media was observed in HuH28 but not in HuCCT-1. To identify the biological significance of periostin in EMT, gene silencing of periostin by small interfering RNA was performed in HuH28 cells. Periostin knockdown in HuH28 cells significantly down-regulated mesenchymal markers and up-regulated epithelial markers, suggesting the reversal of EMT, namely mesenchymal-epithelial transition. Along with these changes, cell proliferation was significantly suppressed by 52%. In addition, cell migration and invasion were significantly suppressed by 62% and 61%, respectively, with reduced gene expression of matrix metalloproteinase 2. Interestingly, chemosensitivity to gemcitabine was also significantly improved by periostin depletion. Conclusion: Periostin plays an important role in the regulation of malignant potential through EMT and is suggested to be a novel target for the treatment of ICC. (Hepatology Communications 2017;1:1099-1109).

Project description:UnlabelledIntrahepatic cholangiocellular carcinoma (ICC) is the second most common type of primary liver cancer. However, its tumor heterogeneity and molecular characteristics are largely unknown. In this study, we conducted transcriptomic profiling of 23 ICC and combined hepatocellular cholangiocarcinoma tumor specimens from Asian patients using Affymetrix messenger RNA (mRNA) and NanoString microRNA microarrays to search for unique gene signatures linked to tumor subtypes and patient prognosis. We validated the signatures in an additional 68 ICC cases derived from Caucasian patients. We found that both mRNA and microRNA expression profiles could independently classify Asian ICC cases into two main subgroups, one of which shared gene expression signatures with previously identified hepatocellular carcinoma (HCC) with stem cell gene expression traits. ICC-specific gene signatures could predict survival in Asian HCC cases and independently in Caucasian ICC cases. Integrative analyses of the ICC-specific mRNA and microRNA expression profiles revealed that a common signaling pathway linking miR-200c signaling to epithelial-mesenchymal transition (EMT) was preferentially activated in ICC with stem cell gene expression traits. Inactivation of miR-200c resulted in an induction of EMT, whereas activation of miR-200c led to a reduction of EMT including a reduced cell migration and invasion in ICC cells. We also found that miR-200c and neural cell adhesion molecule 1 (NCAM1) expression were negatively correlated and their expression levels were predictive of survival in ICC samples. NCAM1, a known hepatic stem/progenitor cell marker, was experimentally demonstrated to be a direct target of miR-200c.ConclusionOur results indicate that ICC and HCC share common stem-like molecular characteristics and poor prognosis. We suggest that the specific components of EMT may be exploited as critical biomarkers and clinically relevant therapeutic targets for an aggressive form of stem cell-like ICC.

Dataset Information

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

Background

Methods

Results

Conclusions

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets