Transcriptional census of 36 microdissected colorectal cancers yields a gene signature to distinguish UICC II and III
Corresponding Author
Joern Groene
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Joern Groene and Ullrich Mansmann share first authorship.
Joern Groene, Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Hindenburgdamm 30, D-12200 Berlin, Germany
Ulrich Mansmann, Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians Universität Muenchen, Marchionistraße 15, D-81377 München, Germany
Search for more papers by this authorCorresponding Author
Ulrich Mansmann
Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians University München, München, Germany
Joern Groene and Ullrich Mansmann share first authorship.
Joern Groene, Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Hindenburgdamm 30, D-12200 Berlin, Germany
Ulrich Mansmann, Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians Universität Muenchen, Marchionistraße 15, D-81377 München, Germany
Search for more papers by this authorReinhard Meister
Department II, University of Applied Sciences, Berlin, Germany
Search for more papers by this authorEike Staub
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany
Search for more papers by this authorStefan Roepcke
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany
Search for more papers by this authorMaya Heinze
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorIrina Klaman
Department of Pathology, HELIOS Klinikum Emil von Behring, Berlin, Germany
Search for more papers by this authorThomas Brümmendorf
Novartis Institutes for Biomedical Research, Basel, Switzerland
Search for more papers by this authorKlaus Hermann
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorChristoph Loddenkemper
Institute of Pathology, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorChristian Pilarsky
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Dresden, Dresden, Germany
Search for more papers by this authorBenno Mann
Department of Surgery, Augusta-Kranken-Anstalt GmbH, Bochum, Germany
Search for more papers by this authorHans-Peter Adams
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorHeinz Johannes Buhr
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorAndré Rosenthal
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorCorresponding Author
Joern Groene
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Joern Groene and Ullrich Mansmann share first authorship.
Joern Groene, Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Hindenburgdamm 30, D-12200 Berlin, Germany
Ulrich Mansmann, Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians Universität Muenchen, Marchionistraße 15, D-81377 München, Germany
Search for more papers by this authorCorresponding Author
Ulrich Mansmann
Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians University München, München, Germany
Joern Groene and Ullrich Mansmann share first authorship.
Joern Groene, Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Hindenburgdamm 30, D-12200 Berlin, Germany
Ulrich Mansmann, Institute for Medical Informatics, Biometry, and Epidemiology, Ludwig Maximillians Universität Muenchen, Marchionistraße 15, D-81377 München, Germany
Search for more papers by this authorReinhard Meister
Department II, University of Applied Sciences, Berlin, Germany
Search for more papers by this authorEike Staub
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany
Search for more papers by this authorStefan Roepcke
Department of Computational Molecular Biology, Max Planck Institute for Molecular Genetics, Berlin, Germany
Search for more papers by this authorMaya Heinze
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorIrina Klaman
Department of Pathology, HELIOS Klinikum Emil von Behring, Berlin, Germany
Search for more papers by this authorThomas Brümmendorf
Novartis Institutes for Biomedical Research, Basel, Switzerland
Search for more papers by this authorKlaus Hermann
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorChristoph Loddenkemper
Institute of Pathology, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorChristian Pilarsky
Department of Visceral, Thoracic and Vascular Surgery, University Hospital Dresden, Dresden, Germany
Search for more papers by this authorBenno Mann
Department of Surgery, Augusta-Kranken-Anstalt GmbH, Bochum, Germany
Search for more papers by this authorHans-Peter Adams
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorHeinz Johannes Buhr
Department of General, Vascular and Thoracic Surgery, Campus Benjamin Franklin, Charité Universitaetsmedizin, Berlin, Germany
Search for more papers by this authorAndré Rosenthal
Signature Diagnostics AG, Voltaireweg 4B, Potsdam, Germany
Search for more papers by this authorAbstract
UICC stage II and III colorectal cancers (CRC) differ fundamentally in prognosis and therapeutic concepts. To analyze differential gene expression between both stages and to establish a relationship between molecular background and clinical presentation, tumor material from 36 unselected consecutive patients presenting with sporadic CRC, 18 UICC stage II and 18 UICC stage III, were laser microdissected to separate epithelial tumor cells. Gene expression levels were measured using U133A Affymetrix gene arrays. Twelve CRC associated signal transduction pathways as well as all 22,000 probe sets were screened for differential gene expression. We identified a signature consisting of 45 probe sets that allowed discrimination between UICC stage II and stage III with a rate of correct classification of about 80%. The most distinctive elements in this signature were the gene GSTP-binding elongation factor (GSPT2) and the transcription factor HOXA9. Differential expression of these genes was confirmed by quantitative real-time polymerase chain reaction (p(HOXA9) = 0.04, p(GSTP2) = 0.02). Despite the reliability of the presented data, there was no substantial differential expression of genes in cancer-related pathways. However, the comparison with recently published data corroborates the 45 gene signature showing structural agreement in the direction of fold changes of gene expression levels for our set of genes chosen to discriminate between both stages. © 2006 Wiley-Liss, Inc.
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