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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2014
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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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1613136137945088000 |