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Gene expression profiles in stages II and III colon cancers: application of a 128-gene signature

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International Journal of Colorectal Disease Aims and scope Submit manuscript

Abstract

Purpose

A 128-gene signature has been proposed to predict outcome in patients with stages II and III colorectal cancers. In the present study, we aimed to reproduce and validate the 128-gene signature in external and independent material.

Methods

Gene expression data from the original material were retrieved from the Gene Expression Omnibus (GEO) (n = 111) in addition to a Danish data set (n = 37). All patients had stages II and III colon cancers. A Prediction Analysis of Microarray classifier, based on the 128-gene signature and the original training set of stage I (n = 65) and stage IV (n = 76) colon cancers, was reproduced. The stages II and III colon cancers were subsequently classified as either stage I-like (good prognosis) or stage IV-like (poor prognosis) and assessed by the 36 months cumulative incidence of relapse.

Results

In the GEO data set, results were reproducible in stage III, as patients predicted to be stage I-like had a significant lower risk of relapse than patients predicted as stage IV-like (P = 0.04, Gray test). Results were not reproducible in stage II patients (P > 0.05, Gray test). In the Danish data set, two of four stage III patients with relapse were correctly predicted as stage IV-like, and the remaining patients were predicted as stage I-like and unclassifiable, respectively. Stage II patients could not be stratified.

Conclusions

The 128-gene signature showed reproducibility in stage III colon cancer, but could not predict recurrence in stage II. Individual patient predictions in an independent Danish material were unsatisfactory. Additional validation in larger cohorts is warranted.

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Acknowledgments

This work was supported by Region Zealand Research grant, the Beckett Foundation, the Health Science Foundation of Eastern Denmark, the Hartmanns Family Foundation, and the Alfred Nielsen and Wife's Foundation. Special thanks go to Liselotte Laustsen for technical and laboratory assistance.

Conflict of interest

The authors declare no conflicts of interest.

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Authors and Affiliations

  1. Department of Surgery, Roskilde Hospital, Faculty of Health Sciences, University of Copenhagen, Koegevej 7-13, 4000, Roskilde, Denmark

    Morten Thorsteinsson, Lene T. Kirkeby & Per Jess

  2. Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of Copenhagen, Roskilde, Denmark

    Morten Thorsteinsson, Raino Hansen, Leif R. Lund & Jørgen Olsen

  3. Department of Surgery K, Bispebjerg Hospital, Faculty of Health Sciences, University of Copenhagen, Roskilde, Denmark

    Lars T. Sørensen

  4. Department of Biostatistics, Faculty of Health Sciences, University of Copenhagen, Roskilde, Denmark

    Thomas A. Gerds

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  1. Morten Thorsteinsson
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Correspondence to Morten Thorsteinsson.

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Thorsteinsson, M., Kirkeby, L.T., Hansen, R. et al. Gene expression profiles in stages II and III colon cancers: application of a 128-gene signature. Int J Colorectal Dis 27, 1579–1586 (2012). https://doi.org/10.1007/s00384-012-1517-4

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