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Genomic characterization of liver metastases from colorectal cancer patients

Metastatic 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 eval...

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Autores principales: Sayagués, José María, Corchete, Luís Antonio, Gutiérrez, María Laura, Sarasquete, Maria Eugenia, del Mar Abad, María, Bengoechea, Oscar, Fermiñán, Encarna, Anduaga, María Fernanda, del Carmen, Sofia, Iglesias, Manuel, Esteban, Carmen, Angoso, María, Alcazar, Jose Antonio, García, Jacinto, Orfao, Alberto, Muñoz-Bellvis, Luís
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341953/
https://www.ncbi.nlm.nih.gov/pubmed/27662660
http://dx.doi.org/10.18632/oncotarget.12140
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author Sayagués, José María
Corchete, Luís Antonio
Gutiérrez, María Laura
Sarasquete, Maria Eugenia
del Mar Abad, María
Bengoechea, Oscar
Fermiñán, Encarna
Anduaga, María Fernanda
del Carmen, Sofia
Iglesias, Manuel
Esteban, Carmen
Angoso, María
Alcazar, Jose Antonio
García, Jacinto
Orfao, Alberto
Muñoz-Bellvis, Luís
author_facet Sayagués, José María
Corchete, Luís Antonio
Gutiérrez, María Laura
Sarasquete, Maria Eugenia
del Mar Abad, María
Bengoechea, Oscar
Fermiñán, Encarna
Anduaga, María Fernanda
del Carmen, Sofia
Iglesias, Manuel
Esteban, Carmen
Angoso, María
Alcazar, Jose Antonio
García, Jacinto
Orfao, Alberto
Muñoz-Bellvis, Luís
author_sort Sayagués, José María
collection PubMed
description Metastatic 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.
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spelling pubmed-53419532017-03-27 Genomic characterization of liver metastases from colorectal cancer patients Sayagués, José María Corchete, Luís Antonio Gutiérrez, María Laura Sarasquete, Maria Eugenia del Mar Abad, María Bengoechea, Oscar Fermiñán, Encarna Anduaga, María Fernanda del Carmen, Sofia Iglesias, Manuel Esteban, Carmen Angoso, María Alcazar, Jose Antonio García, Jacinto Orfao, Alberto Muñoz-Bellvis, Luís Oncotarget Research Paper Metastatic 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. Impact Journals LLC 2016-09-20 /pmc/articles/PMC5341953/ /pubmed/27662660 http://dx.doi.org/10.18632/oncotarget.12140 Text en Copyright: © 2016 Sayagués et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Sayagués, José María
Corchete, Luís Antonio
Gutiérrez, María Laura
Sarasquete, Maria Eugenia
del Mar Abad, María
Bengoechea, Oscar
Fermiñán, Encarna
Anduaga, María Fernanda
del Carmen, Sofia
Iglesias, Manuel
Esteban, Carmen
Angoso, María
Alcazar, Jose Antonio
García, Jacinto
Orfao, Alberto
Muñoz-Bellvis, Luís
Genomic characterization of liver metastases from colorectal cancer patients
title Genomic characterization of liver metastases from colorectal cancer patients
title_full Genomic characterization of liver metastases from colorectal cancer patients
title_fullStr Genomic characterization of liver metastases from colorectal cancer patients
title_full_unstemmed Genomic characterization of liver metastases from colorectal cancer patients
title_short Genomic characterization of liver metastases from colorectal cancer patients
title_sort genomic characterization of liver metastases from colorectal cancer patients
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5341953/
https://www.ncbi.nlm.nih.gov/pubmed/27662660
http://dx.doi.org/10.18632/oncotarget.12140
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