Hass HG, Nehls O, Jobst J, Frilling A, Vogel U, Kaiser S. Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis. World J Gastroenterol 2008; 14(16): 2501-2510 [PMID: 18442196 DOI: 10.3748/wjg.14.2501]
Corresponding Author of This Article
Holger G Hass, Department of Oncology, Hematology and Palliative Care, Marien Hospital, Boeheim-Street 37, Stuttgart 70199, Germany. holgerhass@vinzenz.de
Article-Type of This Article
Clinical Research
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World J Gastroenterol. Apr 28, 2008; 14(16): 2501-2510 Published online Apr 28, 2008. doi: 10.3748/wjg.14.2501
Identification of osteopontin as the most consistently over-expressed gene in intrahepatic cholangiocarcinoma: Detection by oligonucleotide microarray and real-time PCR analysis
Holger G Hass, Oliver Nehls, Juergen Jobst, Andrea Frilling, Ulrich Vogel, Stephan Kaiser
Holger G Hass, Department of Oncology, Hematology and Palliative Care, Marien Hospital Stuttgart, Stuttgart 70199, Germany
Oliver Nehls, Department of Hematology, Oncology and Rheumatology, University of Tuebingen, Tuebingen 72076, Germany
Andrea Frilling, Department of Abdominal and Transplant Surgery, University of Essen, Essen 45127, Germany
Ulrich Vogel, Department of Pathology, University of Tuebingen, Tuebingen 72076, Germany
Stephan Kaiser, Department of Gastroenterology, Hepatology and Infectious Diseases, University of Tuebingen, Tuebingen 72076, Germany
Author contributions: Hass HG and Nehls O contributed equally to this work; Hass HG, Jobst J, and Kaiser S designed the research; Hass HG and Jobst J performed the research; Frilling A contributed tumor probes and biopsies; Vogel U performed the pathological studies and immunohistochemistry staining experiments; Hass HG and Nehls O analyzed the data; and Hass HG and Kaiser S wrote the paper.
Correspondence to: Holger G Hass, Department of Oncology, Hematology and Palliative Care, Marien Hospital, Boeheim-Street 37, Stuttgart 70199, Germany. holgerhass@vinzenz.de
Telephone: +49-711-64898101
Fax: +49-711-64898102
Received: October 22, 2007 Revised: February 18, 2008 Published online: April 28, 2008
Abstract
AIM: To investigate the molecular pathways involved in human cholangiocarcinogenesis by gene expression profiling.
METHODS: Oligonucleotide arrays (Affymetrix U133A) were used to establish a specific gene expression profile of intrahepatic CCC in comparison to corresponding non-malignant liver tissue. To validate the expression values of the most overexpressed genes, RT-PCR experiments were performed.
RESULTS: Five hundred and fifty-two statistically differentially expressed genes/ESTs (221 probes significantly up-regulated, 331 probes down-regulated; P < 0.05; fold change > 2; ≥ 70%) were identified. Using these data and two-dimensional cluster analysis, a specific gene expression profile was obtained allowing fast and reproducible differentiation of CCC, which was confirmed by supervised neuronal network modelling. The most consistently overexpressed gene (median fold change 33.5, significantly overexpressed in 100%) encoded osteopontin. Furthermore, an association of various genes with the histopathological grading could be demonstrated.
CONCLUSION: A highly specific gene expression profile for intrahepatic CCC was identified, allowing for its fast and reproducible discrimination against non-malignant liver tissue and other liver masses. The most overexpressed gene in intrahepatic CCC was the gene encoding osteopontin. These data may lead to a better understanding of human cholangiocarcinogenesis.
