Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

BMC Cancer

Research Article

Eun-Kyung Ahn¹  Sun-Hee Leem¹  Baik-Hwan Cho²  Dae-Ghon Kim³  Goung-Ran Yu³  Mi-Jin Lee³  Xiang-Dan Cui³  Min-A Seol³  In-Sun Chu⁴  In-Hee Kim⁵ 

[1] Department of Biological Science, Dong-A University, 604-714, Busan, South Korea;Department of Surgery, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea;Division of Gastroenterology and Hepatology, the Institute for Medical Science, Departments of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea;Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, 305-806, Daejeon, South Korea;null;

关键词: Cholangiocarcinoma;    Choledochal Cyst;    Biliary Tract Cancer;    Biliary Epithelial Cell;    Unsupervised Hierarchical Cluster Analysis;   

DOI  :  10.1186/1471-2407-11-78

 received in 2009-12-12, accepted in 2011-02-19,  发布年份 2011

来源: Springer

【 摘 要 】

BackgroundThe molecular mechanisms of CC (cholangiocarcinoma) oncogenesis and progression are poorly understood. This study aimed to determine the genome-wide expression of genes related to CC oncogenesis and sarcomatous transdifferentiation.MethodsGenes that were differentially expressed between CC cell lines or tissues and cultured normal biliary epithelial (NBE) cells were identified using DNA microarray technology. Expressions were validated in human CC tissues and cells.ResultsUsing unsupervised hierarchical clustering analysis of the cell line and tissue samples, we identified a set of 342 commonly regulated (>2-fold change) genes. Of these, 53, including tumor-related genes, were upregulated, and 289, including tumor suppressor genes, were downregulated (<0.5 fold change). Expression of SPP1, EFNB2, E2F2, IRX3, PTTG1, PPARγ, KRT17, UCHL1, IGFBP7 and SPARC proteins was immunohistochemically verified in human and hamster CC tissues. Additional unsupervised hierarchical clustering analysis of sarcomatoid CC cells compared to three adenocarcinomatous CC cell lines revealed 292 differentially upregulated genes (>4-fold change), and 267 differentially downregulated genes (<0.25 fold change). The expression of 12 proteins was validated in the CC cell lines by immunoblot analysis and immunohistochemical staining. Of the proteins analyzed, we found upregulation of the expression of the epithelial-mesenchymal transition (EMT)-related proteins VIM and TWIST1, and restoration of the methylation-silenced proteins LDHB, BNIP3, UCHL1, and NPTX2 during sarcomatoid transdifferentiation of CC.ConclusionThe deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis.

【 授权许可】

Unknown   
© Seol et al; licensee BioMed Central Ltd. 2011. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.