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Molecular Cancer
Published in: Molecular Cancer 1/2014

Open Access 01-12-2014 | Research

Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer

Authors: Rebeca Sanz-Pamplona, Antoni Berenguer, David Cordero, David G Molleví, Marta Crous-Bou, Xavier Sole, Laia Paré-Brunet, Elisabet Guino, Ramón Salazar, Cristina Santos, Javier de Oca, Xavier Sanjuan, Francisco Rodriguez-Moranta, Victor Moreno

Published in: Molecular Cancer | Issue 1/2014

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Abstract

Background

A colorectal tumor is not an isolated entity growing in a restricted location of the body. The patient’s gut environment constitutes the framework where the tumor evolves and this relationship promotes and includes a complex and tight correlation of the tumor with inflammation, blood vessels formation, nutrition, and gut microbiome composition. The tumor influence in the environment could both promote an anti-tumor or a pro-tumor response.

Methods

A set of 98 paired adjacent mucosa and tumor tissues from colorectal cancer (CRC) patients and 50 colon mucosa from healthy donors (246 samples in total) were included in this work. RNA extracted from each sample was hybridized in Affymetrix chips Human Genome U219. Functional relationships between genes were inferred by means of systems biology using both transcriptional regulation networks (ARACNe algorithm) and protein-protein interaction networks (BIANA software).

Results

Here we report a transcriptomic analysis revealing a number of genes activated in adjacent mucosa from CRC patients, not activated in mucosa from healthy donors. A functional analysis of these genes suggested that this active reaction of the adjacent mucosa was related to the presence of the tumor. Transcriptional and protein-interaction networks were used to further elucidate this response of normal gut in front of the tumor, revealing a crosstalk between proteins secreted by the tumor and receptors activated in the adjacent colon tissue; and vice versa. Remarkably, Slit family of proteins activated ROBO receptors in tumor whereas tumor-secreted proteins transduced a cellular signal finally activating AP-1 in adjacent tissue.

Conclusions

The systems-level approach provides new insights into the micro-ecology of colorectal tumorogenesis. Disrupting this intricate molecular network of cell-cell communication and pro-inflammatory microenvironment could be a therapeutic target in CRC patients.
Appendix
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Metadata
Title
Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer
Authors
Rebeca Sanz-Pamplona
Antoni Berenguer
David Cordero
David G Molleví
Marta Crous-Bou
Xavier Sole
Laia Paré-Brunet
Elisabet Guino
Ramón Salazar
Cristina Santos
Javier de Oca
Xavier Sanjuan
Francisco Rodriguez-Moranta
Victor Moreno
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Molecular Cancer / Issue 1/2014
Electronic ISSN: 1476-4598
DOI
https://doi.org/10.1186/1476-4598-13-46

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