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

BMC Cancer - Tập 11 Số 1 - 2011
Min-A Seol1, In-Sun Chu2, Mi-Jin Lee1, Goung-Ran Yu1, Xiang-Dan Cui1, Baik-Hwan Cho3, Eun‐Kyung Ahn4, Sun‐Hee Leem4, In-Hee Kim1, Dae‐Ghon Kim1
1Division of Gastroenterology and Hepatology, the Institute for Medical Science, Departments of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea
2Medical Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, 305-806, South Korea
3Department of Surgery, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea
4Department of Biological Science, Dong-A University, Busan 604-714, South Korea

Tóm tắt

Abstract Background The 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. Methods Genes 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. Results Using 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. Conclusion The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis.

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Tài liệu tham khảo

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