A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer

Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC) was developed. Its predictive value was validated in datasets GSE...

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Main Authors: Berdiel-Acer, Mireia, Berenguer, Antoni, Sanz-Pamplona, Rebeca, Cuadras, Daniel, Sanjuan, Xavier, Paules, Maria José, Santos, Cristina, Salazar, Ramon, Moreno, Victor, Capella, Gabriel, Villanueva, Alberto, Molleví, David G.
Format: Online
Language:English
Published: Impact Journals LLC 2014
Online Access:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171642/
id pubmed-4171642
recordtype oai_dc
spelling pubmed-41716422014-09-23 A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer Berdiel-Acer, Mireia Berenguer, Antoni Sanz-Pamplona, Rebeca Cuadras, Daniel Sanjuan, Xavier Paules, Maria José Santos, Cristina Salazar, Ramon Moreno, Victor Capella, Gabriel Villanueva, Alberto Molleví, David G. Research Paper Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR. The 5-gene classifier was significantly associated with increased relapse risk and death from CRC across all validation series of Stage II/III patients used. Multivariate Cox regression analyses confirmed the independent prognostic value of the stromal classifier (HR=2.67; P=0.002). Post-test probabilities provided evidence of the suitability of the 5-gene classifier in clinical practice, identifying a subgroup of Stage-II patients who were at high risk of relapse. Moreover, the a priory worst prognosis mesenchymal subtype of tumours can be stratified according to the physiological status of their carcinoma-associated fibroblasts. In conclusion the CAFs-derived 5-gene classifier provides more accurate information about outcome than conventional clinicopathological criteria and it could be useful to take clinical decisions, especially in Stage II. Additionally, the classifier put into relevance the CAF's intratumoral heterogeneity and might contribute to find relevant targets for depleting adequate CAFS subtypes. Impact Journals LLC 2014-07-23 /pmc/articles/PMC4171642/ /pubmed/25115384 Text en Copyright: © 2014 Berdiel-Acer et al. http://creativecommons.org/licenses/by/2.5/ 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.
repository_type Open Access Journal
institution_category Foreign Institution
institution US National Center for Biotechnology Information
building NCBI PubMed
collection Online Access
language English
format Online
author Berdiel-Acer, Mireia
Berenguer, Antoni
Sanz-Pamplona, Rebeca
Cuadras, Daniel
Sanjuan, Xavier
Paules, Maria José
Santos, Cristina
Salazar, Ramon
Moreno, Victor
Capella, Gabriel
Villanueva, Alberto
Molleví, David G.
spellingShingle Berdiel-Acer, Mireia
Berenguer, Antoni
Sanz-Pamplona, Rebeca
Cuadras, Daniel
Sanjuan, Xavier
Paules, Maria José
Santos, Cristina
Salazar, Ramon
Moreno, Victor
Capella, Gabriel
Villanueva, Alberto
Molleví, David G.
A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
author_facet Berdiel-Acer, Mireia
Berenguer, Antoni
Sanz-Pamplona, Rebeca
Cuadras, Daniel
Sanjuan, Xavier
Paules, Maria José
Santos, Cristina
Salazar, Ramon
Moreno, Victor
Capella, Gabriel
Villanueva, Alberto
Molleví, David G.
author_sort Berdiel-Acer, Mireia
title A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
title_short A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
title_full A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
title_fullStr A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
title_full_unstemmed A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
title_sort 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer
description Based on 108 differentially expressed genes between carcinoma-associated fibroblasts (CAFs) and paired normal colonic fibroblasts we recently reported, a 5-gene classifier for relapse prediction in Stage II/III colorectal cancer (CRC) was developed. Its predictive value was validated in datasets GSE17538, GSE33113 and GSE14095. An additional validation was performed in a metacohort (n=317) and 142 CRC patients by means of RT-PCR. The 5-gene classifier was significantly associated with increased relapse risk and death from CRC across all validation series of Stage II/III patients used. Multivariate Cox regression analyses confirmed the independent prognostic value of the stromal classifier (HR=2.67; P=0.002). Post-test probabilities provided evidence of the suitability of the 5-gene classifier in clinical practice, identifying a subgroup of Stage-II patients who were at high risk of relapse. Moreover, the a priory worst prognosis mesenchymal subtype of tumours can be stratified according to the physiological status of their carcinoma-associated fibroblasts. In conclusion the CAFs-derived 5-gene classifier provides more accurate information about outcome than conventional clinicopathological criteria and it could be useful to take clinical decisions, especially in Stage II. Additionally, the classifier put into relevance the CAF's intratumoral heterogeneity and might contribute to find relevant targets for depleting adequate CAFS subtypes.
publisher Impact Journals LLC
publishDate 2014
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4171642/
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