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dc.contributor.authorSayagués, José María-
dc.contributor.authorCorchete, Luis A.-
dc.contributor.authorGutiérrez, María Laura-
dc.contributor.authorSarasquete, María Eugenia-
dc.contributor.authorAbad, María del Mar-
dc.contributor.authorBengoechea, Óscar-
dc.contributor.authorFermiñán, Encarnación-
dc.contributor.authorAnduaga, María Fernanda-
dc.contributor.authorCarmen, Sofía del-
dc.contributor.authorIglesias, Manuel-
dc.contributor.authorEsteban, Carmen-
dc.contributor.authorAngoso, María-
dc.contributor.authorAlcazar, Jose Antonio-
dc.contributor.authorGarcía, Jacinto-
dc.contributor.authorOrfao, Alberto-
dc.contributor.authorMuñoz-Bellvis, Luís-
dc.identifierdoi: 10.18632/oncotarget.12140-
dc.identifiere-issn: 1949-2553-
dc.identifier.citationOncotarget 7(45): 72908-72922 (2016)-
dc.description.abstractMetastatic dissemination is the most frequent cause of death of sporadic colorectal cancer (sCRC) patients. Genomic abnormalities which are potentially characteristic of such advanced stages of the disease are complex and so far, they have been poorly described and only partially understood. We evaluated the molecular heterogeneity of sCRC tumors based on simultaneous assessment of the overall GEP of both coding mRNA and non-coding RNA genes in primary sCRC tumor samples from 23 consecutive patients and their paired liver metastases. Liver metastases from the sCRC patients analyzed, systematically showed deregulated transcripts of those genes identified as also deregulated in their paired primary colorectal carcinomas. However, some transcripts were found to be specifically deregulated in liver metastases (vs. non-tumoral colorectal tissues) while expressed at normal levels in their primary tumors, reflecting either an increased genomic instability of metastatic cells or theiradaption to the liver microenvironment. Newly deregulated metastatic transcripts included overexpression of APOA1, HRG, UGT2B4, RBP4 and ADH4 mRNAS and the miR-3180-3p, miR-3197, miR-3178, miR-4793 and miR-4440 miRNAs, together with decreased expression of the IGKV1-39, IGKC, IGKV1-27, FABP4 and MYLK mRNAS and the miR-363, miR-1, miR-143, miR-27b and miR-28-5p miRNAs. Canonical pathways found to be specifically deregulated in liver metastatic samples included multiple genes related with intercellular adhesion and the metastatic processes (e.g., IGF1R, PIK3CA, PTEN and EGFR), endocytosis (e.g., the PDGFRA, SMAD2, ERBB3, PML and FGFR2), and the cell cycle (e.g., SMAD2, CCND2, E2F5 and MYC). Our results also highlighted the activation of genes associated with the TGFβ signaling pathway, -e.g. RHOA, SMAD2, SMAD4, SMAD5, SMAD6, BMPR1A, SMAD7 and MYC-, which thereby emerge as candidate genes to play an important role in CRC tumor metastasis.-
dc.description.sponsorshipThis work has been partially supported by grants from the Instituto de Salud Carlos III (ISCIII; Ministerio de Sanidad y Consumo, Madrid, Spain) (PI12/02053-FIS), Gerencia Regional de Salud de Castilla y León, Valladolid, Spain (GRS1302/A/16), Consejería de Sanidad (Junta de Castilla y Leon, Valladolid, Spain) (BIO/SA02/13 and BIO/SA46/14), RTICC from the ISCIII (RD12/0020/0035-FEDER, RD12/0036/0048-FEDER), Fundación Memoria de Don Samuel Solórzano Barruso, (Salamanca, Spain) and Fundación Eugenio Rodríguez Pascual, (Madrid, Spain). JM Sayagués and ME Sarasquete are supported by grants (CES11/004 and CP13/00080; respectively) from the ISCIII, Ministerio de Ciencia e Innovación, Madrid, Spain.-
dc.publisherImpact Journals-
dc.relation.isversionofPublisher's version-
dc.subjectColorectal cancer-
dc.titleGenomic characterization of liver metastases from colorectal cancer patients-
dc.description.versionPeer Reviewed-
dc.contributor.funderInstituto de Salud Carlos III-
dc.contributor.funderJunta de Castilla y León-
dc.contributor.funderMinisterio de Ciencia e Innovación (España)-
dc.contributor.funderFundación Eugenio Rodríguez Pascual-
dc.contributor.funderEuropean Commission-
dc.contributor.funderFundación Memoria de D. Samuel Solorzano Barruso-
dc.contributor.funderMinisterio de Sanidad y Consumo (España)-
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