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Transcriptional Profiles of Peripheral Blood Leukocytes Identify Patients with Cholangiocarcinoma and Predict Outcome

  • Subimerb, Chutima (Department of Biochemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Wongkham, Chaisiri (Department of Biochemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University) ;
  • Khuntikeo, Narong (Department of Surgery and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicin, Khon Kaen University) ;
  • Leelayuwat, Chanvit (Department of Immunology, Faculty of Associated Medical Science, and Liver Fluke and Cholangiocarcinoma Research Center, Khon Kaen University) ;
  • McGrath, Michael S. (Department of Laboratory Medicine, University of California San Francisco) ;
  • Wongkham, Sopit (Department of Biochemistry, and Liver Fluke and Cholangiocarcinoma Research Center, Faculty of Medicine, Khon Kaen University)
  • Published : 2014.05.30

Abstract

Cholangiocarcinoma (CCA), a slow growing but highly metastatic tumor, is highly prevalent in Northeast Thailand. Specific tests that predict prognosis of CCA remain elusive. The present study was designed to investigate whether peripheral blood leukocyte (PBL) transcriptional profiles might be of use as a prognostic test in CCA patients. Gene expression profiles of PBLs from 9 CCA and 8 healthy subjects were conducted using the Affymetrix HG_U133 Plus 2.0 GeneChip. We indentified informative PBLs gene expression profiles that could reliably distinguish CCA patients from healthy subjects. Of these CCA specific genes, 117 genes were up regulated and 60 were down regulated. The molecular and cellular functions predicted for these CCA specific genes according to the Gene Ontology database indicated differential PBL expression of host immune response and tumor progression genes (EREG, TGF ${\beta}1$, CXCL2, CXCL3, IL-8, and VEGFA). The expression levels of 9 differentially expressed genes were verified in 36 CCA vs 20 healthy subjects. A set of three tumor invasion related genes (PLAU, CTSL and SERPINB2) computed as "prognostic index" was found to be an independent and statistically significant predictor for CCA patient survival. The present study shows that CCA PBLs may serve as disease predictive clinically accessible surrogates for indentifying expressed genes reflective of CCA disease severity.

Keywords

References

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