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

BMC Cancer

Wolfgang Kemmner²  Miguel A Andrade-Navarro³  Thomas Jöns¹  Matthew R Huska⁴  Marion Fehlker² 

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

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

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

[4]Presently at Department for Computational Molecular Biology, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany

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

Others  :  859093
DOI  :  10.1186/1471-2407-14-64

 received in 2013-02-25, accepted in 2014-01-29,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Fehlker et al.; licensee BioMed Central Ltd.

【 图 表 】

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