Open Access Research article

Concerted down-regulation of immune-system related genes predicts metastasis in colorectal carcinoma

Marion Fehlker1, Matthew R Huska23, Thomas Jöns4, Miguel A Andrade-Navarro2 and Wolfgang Kemmner1*

Author Affiliations

1 Translational Oncology, Experimental Clinical Research Center, Charite Campus Buch, Lindenberger Weg 80, D-13125 Berlin, Germany

2 Computational Biology and Data Mining group, Max Delbrueck Center for Molecular Medicine, Robert Roessle Str. 10, D-13125 Berlin, Germany

3 Presently at Department for Computational Molecular Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany

4 Institut für Integrative Anatomie, Charite Campus Mitte, Philippstr. 12, D-10115 Berlin, Germany

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BMC Cancer 2014, 14:64  doi:10.1186/1471-2407-14-64

Published: 5 February 2014

Abstract

Background

This study aimed at the identification of prognostic gene expression markers in early primary colorectal carcinomas without metastasis at the time point of surgery by analyzing genome-wide gene expression profiles using oligonucleotide microarrays.

Methods

Cryo-conserved tumor specimens from 45 patients with early colorectal cancers were examined, with the majority of them being UICC stage II or earlier and with a follow-up time of 41–115 months. Gene expression profiling was performed using Whole Human Genome 4x44K Oligonucleotide Microarrays. Validation of microarray data was performed on five of the genes in a smaller cohort.

Results

Using a novel algorithm based on the recursive application of support vector machines (SVMs), we selected a signature of 44 probes that discriminated between patients developing later metastasis and patients with a good prognosis. Interestingly, almost half of the genes was related to the patients’ immune response and showed reduced expression in the metastatic cases.

Conclusions

Whereas up to now gene signatures containing genes with various biological functions have been described for prediction of metastasis in CRC, in this study metastasis could be well predicted by a set of gene expression markers consisting exclusively of genes related to the MHC class II complex involved in immune response. Thus, our data emphasize that the proper function of a comprehensive network of immune response genes is of vital importance for the survival of colorectal cancer patients.

Keywords:
Early colorectal cancer; Metastasis; Computational marker analysis; Immune system; Gene expression profiling