Concerted down-regulation of immune-system related genes predicts metastasis in colorectal carcinomaReportar como inadecuado




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BMC Cancer

, 14:64

Systems biology, post-genomic analysis and emerging technologies

Abstract

BackgroundThis 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.

MethodsCryo-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.

ResultsUsing 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.

ConclusionsWhereas 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.

KeywordsEarly colorectal cancer Metastasis Computational marker analysis Immune system Gene expression profiling AbbreviationsCRCColorectal cancer

GOGene ontology

SVMSupport vector machine.

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-14-64 contains supplementary material, which is available to authorized users.

Marion Fehlker, Matthew R Huska contributed equally to this work.

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Autor: Marion Fehlker - Matthew R Huska - Thomas Jöns - Miguel A Andrade-Navarro - Wolfgang Kemmner

Fuente: https://link.springer.com/







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