title: Aberrant gene expression in mucosa adjacent to tumor reveals a molecular crosstalk in colon cancer.
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.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Sanz-Pamplona
authors.forename: Antoni
authors.initials: A
authors.lastname: Berenguer
authors.forename: David
authors.initials: D
authors.lastname: Cordero
authors.forename: David G
authors.initials: DG
authors.lastname: Molleví
authors.forename: Marta
authors.initials: M
authors.lastname: Crous-Bou
authors.forename: Xavier
authors.initials: X
authors.lastname: Sole
authors.forename: Laia
authors.initials: L
authors.lastname: Paré-Brunet
authors.forename: Elisabet
authors.initials: E
authors.lastname: Guino
authors.forename: Ramón
authors.initials: R
authors.lastname: Salazar
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.forename: Javier
authors.initials: J
authors.lastname: de Oca
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuan
authors.forename: Francisco
authors.initials: F
authors.lastname: Rodriguez-Moranta
authors.affiliation: Unit of Biomarkers and Susceptibility, Catalan Institute of Oncology (ICO), Bellvitge Biomedical Research Institute (IDIBELL) and CIBERESP, L'Hospitalet de Llobregat, Barcelona, Spain. v.moreno@iconcologia.net.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
mesh_terms: D016022:Case-Control Studies; D003106:Colon / Q000378:metabolism* / Q000473:pathology; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D046228:Microarray Analysis; D025941:Protein Interaction Mapping; D020543:Proteome; D040901:Proteomics; D020239:Receptor Cross-Talk; D015398:Signal Transduction; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000378:metabolism; D059016:Tumor Microenvironment / Q000235:genetics*
chemical_list: D020690:GTPase-Activating Proteins; D020543:Proteome; D018808:Transcription Factor AP-1