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 GS...

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Bibliographic Details
Published in:Oncotarget 2014-08, Vol.5 (15), p.6437-6452
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: Article
Language:English
Subjects:
Aged
Cohort Studies
Colorectal Neoplasms - classification
Colorectal Neoplasms - genetics
Colorectal Neoplasms - pathology
Disease-Free Survival
Female
Fibroblasts - metabolism
Fibroblasts - pathology
Gene Expression
Humans
Male
Middle Aged
Prognosis
Real-Time Polymerase Chain Reaction
Research Paper
Transcriptome
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Summary: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.
ISSN:1949-2553
1949-2553
DOI:10.18632/oncotarget.2237