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Classification of Dukes' B and C colorectal cancers using expression arrays

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Abstract

Purpose

Colorectal cancer is one of the most common malignancies. Substaging of the cancer is of importance not only to prognosis but also to treatment. Classification of substages based on DNA microarray technology is currently the most promising approach. We therefore investigated if gene expression microarrays could be used to classify colorectal tumors.

Methods

We used the Affymetrix oligonucleotide arrays to analyze the expression of more than 5,000 genes in samples from the sigmoid and upper rectum of the left colon. Five samples were from normal mucosa and five samples from each of the Dukes' stages A, B, C, and D. Expression data were filtered based on either covariance or a selection of the most significantly varying genes between tumor stages.

Results

A nearest neighbor classifier was used to classify normal, and Dukes' B and C samples with less than 20% error, whereas Dukes' A and D could not be classified correctly. A number of interesting gene clusters showed a discriminating difference between Dukes' B and C samples. These included mitochondrial genes, stromal remodeling genes, and genes related to cell adhesion.

Conclusion

Molecular classification based on gene expression of one of the most common malignancies, colorectal cancer, now seems to be within reach. The data indicates that it is possible at least to classify Dukes' B and C colorectal tumors with microarrays.

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Fig. 1.
Fig. 2A–D.
Fig. 3A,B.

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Abbreviations

SAM:

Significance analysis of microarrays

FDR:

False discovery rate

RT-PCR:

Real-time polymerase chain reaction

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Acknowledgements

We thank Bente Devantier and Hanne Steen for excellent technical assistance.

Author information

Authors and Affiliations

  1. Dept. of Clinical Biochemistry, Aarhus University Hospital, 8200, Skejby, Aarhus N, Denmark

    Casper Møller Frederiksen & Torben F. Ørntoft

  2. Center for Biological Sequence Analysis, BioCentrum-DTU, Technical University of Denmark, Building 208, 2800, Lyngby, Denmark

    Steen Knudsen

  3. Surgical Research Unit 900, Department of Surgery L, Aarhus University Hospital, Aarhus Amtssygehus, Aarhus, Denmark

    Søren Laurberg

Authors
  1. Casper Møller Frederiksen
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  2. Steen Knudsen
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  3. Søren Laurberg
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  4. Torben F. Ørntoft
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Corresponding author

Correspondence to Torben F. Ørntoft.

Additional information

This work was Supported by the Karen Elise Jensen Foundation, Nordic Cancer Union, Danish Research Council, University of Aarhus, and Novo Nordic. Steen Knudsen was supported by the Danish National Research Foundation.

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Frederiksen, C.M., Knudsen, S., Laurberg, S. et al. Classification of Dukes' B and C colorectal cancers using expression arrays. J Cancer Res Clin Oncol 129, 263–271 (2003). https://doi.org/10.1007/s00432-003-0434-x

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  • DOI: https://doi.org/10.1007/s00432-003-0434-x

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