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

Molecular Cancer

Research

Francisco Rodriguez-Moranta¹  Javier de Oca²  Xavier Sanjuan³  David G Molleví⁴  Ramón Salazar⁵  Cristina Santos⁵  Marta Crous-Bou⁶  David Cordero⁶  Laia Paré-Brunet⁶  Rebeca Sanz-Pamplona⁶  Xavier Sole⁶  Elisabet Guino⁶  Antoni Berenguer⁶  Victor Moreno⁷ 

[1] Department of Gastroenterology, University Hospital Bellvitge (HUB–IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;General and Digestive Surgery Service, University Hospital Bellvitge (HUB–IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), L’Hospitalet de Llobregat, Av. Gran Vía 199-203, 08908, Barcelona, Spain;Pathology Service, University Hospital Bellvitge (HUB–IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Translational Research Lab, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Translational Research Lab, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Medical Oncology Service, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL), L’Hospitalet de Llobregat, Barcelona, Spain;Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L’Hospitalet de Llobregat, Barcelona, Spain;Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L’Hospitalet de Llobregat, Barcelona, Spain;Department of Clinical Sciences, Faculty of Medicine, University of Barcelona (UB), L’Hospitalet de Llobregat, Av. Gran Vía 199-203, 08908, Barcelona, Spain;

关键词: Colorectal cancer;    Network;    Microenvironment;    Molecular crosstalk;    Systems biology;   

DOI  :  10.1186/1476-4598-13-46

 received in 2013-10-14, accepted in 2014-02-19,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundA 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.MethodsA 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).ResultsHere 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.ConclusionsThe 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.

【 授权许可】

Unknown   
© Sanz-Pamplona et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.