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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Detalles Bibliográficos
Autores: Berdiel Acer, Mireia, Berenguer, Antoni, Sanz Pamplona, Rebeca, Cuadras, Daniel, Sanjuan, Xavier, Paules, María José, Santos, Cristina, Salazar Soler, Ramón, Moreno Aguado, Víctor, Capellá, G. (Gabriel), Villanueva Garatachea, Alberto, Molleví, David G.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2014
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:2445/178753
Acceso en línea:https://hdl.handle.net/2445/178753
Access Level:acceso abierto
Palabra clave:Càncer colorectal
Fibroblasts
Genètica
Metabolisme
Colorectal cancer
Genetics
Metabolism
Descripción
Sumario: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.