title: A 5-gene classifier from the carcinoma-associated fibroblast transcriptomic profile and clinical outcome in colorectal cancer.
abstract: 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.
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Mireia
authors.initials: M
authors.lastname: Berdiel-Acer
authors.affiliation: Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Antoni
authors.initials: A
authors.lastname: Berenguer
authors.affiliation: Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Rebeca
authors.initials: R
authors.lastname: Sanz-Pamplona
authors.affiliation: Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Daniel
authors.initials: D
authors.lastname: Cuadras
authors.affiliation: Pathology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Xavier
authors.initials: X
authors.lastname: Sanjuan
authors.affiliation: Pathology Department, Hospital Universitari de Bellvitge, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Maria José
authors.initials: MJ
authors.lastname: Paules
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santos
authors.affiliation: Medical Oncology Department, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Salazar
authors.affiliation: Biomarkers and Susceptibility Unit, Cancer Prevention and Monitoring Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Victor
authors.initials: V
authors.lastname: Moreno
authors.affiliation: Hereditary Colorectal Cancer Programme, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Capella
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: Alberto
authors.initials: A
authors.lastname: Villanueva
authors.affiliation: Translational Research Laboratory, Catalan Institute of Oncology, IDIBELL, L'Hospitalet de Llobregat, Catalonia, Spain.
authors.forename: David G
authors.initials: DG
authors.lastname: Molleví
mesh_terms: D000368:Aged; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000145:classification* / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction; D059467:Transcriptome