title: Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma.
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.
  
  
  CONCLUSIONS
  The deregulation of oncogenes, tumor suppressor genes, and methylation-related genes may be useful in identifying molecular targets for CC diagnosis and prognosis.
authors.affiliation: Division of Gastroenterology and Hepatology, Institute for Medical Science, Department of Internal Medicine, Chonbuk National University Medical School and Hospital, Jeonju, Jeonbuk, South Korea.
authors.forename: Min-A
authors.initials: MA
authors.lastname: Seol
authors.forename: In-Sun
authors.initials: IS
authors.lastname: Chu
authors.forename: Mi-Jin
authors.initials: MJ
authors.lastname: Lee
authors.forename: Goung-Ran
authors.initials: GR
authors.lastname: Yu
authors.forename: Xiang-Dan
authors.initials: XD
authors.lastname: Cui
authors.forename: Baik-Hwan
authors.initials: BH
authors.lastname: Cho
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Ahn
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Leem
authors.forename: In-Hee
authors.initials: IH
authors.lastname: Kim
authors.forename: Dae-Ghon
authors.initials: DG
authors.lastname: Kim
mesh_terms: D000818:Animals; D001650:Bile Duct Neoplasms / Q000235:genetics* / Q000473:pathology*; D001653:Bile Ducts, Intrahepatic / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D054338:Cell Transdifferentiation / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D018281:Cholangiocarcinoma / Q000235:genetics* / Q000473:pathology*; D006224:Cricetinae; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis; D012509:Sarcoma / Q000235:genetics / Q000473:pathology*; D054928:Validation Studies as Topic