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Published in: International Journal of Colorectal Disease 5/2005

01-09-2005 | Original Article

Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression

Authors: Jan Friederichs, Robert Rosenberg, Joerg Mages, Klaus-Peter Janssen, Christian Maeckl, Hjalmar Nekarda, Bernhard Holzmann, Joerg-Ruediger Siewert

Published in: International Journal of Colorectal Disease | Issue 5/2005

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Abstract

Background and aims

Colorectal cancer is one of the leading causes of cancer deaths in the Western world. A better understanding of the development and progression of colorectal carcinoma is needed to define novel targets and strategies for treatment.

Patients/methods

Gene expression profiles were determined for primary tumors of 10 locally restricted (T3N0M0), 8 lymphatically metastasized (T3N+M0), 7 systemically metastasized (T3N+M1) colorectal carcinomas, and 6 specimens of normal colorectal tissue by histology-guided oligonucleotide microarray analysis.

Results

A total of 1,995 genes were differently regulated in primary tumors of colorectal carcinoma compared with normal colorectal tissue. Besides common features of dedifferentiation and different expression of genes involved in cell division, cell adhesion, angiogenesis, signal transduction and metabolism we observed a deregulation of genes with an as yet unclear function. We identified 126 genes that were subsequently up- and 204 genes down-regulated during tumor progression. Furthermore, we found a cluster of five genes exclusively up-regulated in primary tumors of systemically metastasized colorectal carcinomas. A comparison of locally restricted (T3N0M0) and systemically metastasized (T3N+M1) primary tumors showed 50 deregulated genes with a massive down-regulation of immune-modulatory genes in primary tumors of systemically metastasized carcinomas. Primary tumors of lymphatically (T3N+M0) and systemically metastasized (T3N+M1) carcinomas differed in the expression of 19 genes.

Conclusion

These results provide an additional step toward the identification of crucial genes for the progression of colorectal cancer and the identification of novel treatment targets or strategies.
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Metadata
Title
Gene expression profiles of different clinical stages of colorectal carcinoma: toward a molecular genetic understanding of tumor progression
Authors
Jan Friederichs
Robert Rosenberg
Joerg Mages
Klaus-Peter Janssen
Christian Maeckl
Hjalmar Nekarda
Bernhard Holzmann
Joerg-Ruediger Siewert
Publication date
01-09-2005
Publisher
Springer-Verlag
Published in
International Journal of Colorectal Disease / Issue 5/2005
Print ISSN: 0179-1958
Electronic ISSN: 1432-1262
DOI
https://doi.org/10.1007/s00384-004-0722-1

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