Carcinoma-associated fibroblasts’ transcriptomic program predicts clinical outcome in stage II/III colorectal cancer

ABSTRACT: We obtained fibroblast cultures from fresh surgical specimen ressected from patients with primary colorectal carcinoma: normal colonic fibroblasts (NCF=9) from the normal colonic mucosa at least 5-10cm from the surgical margin, carcinoma-associated fibroblasts from the primary tumor (CAF-PT=14) and carcinoma-associated fibroblasts (CAF-LM=11) from fresh surgical specimens of liver metastases. We identified 277 probes, in common between the three types of fibroblasts, whose expression level is sequentially deregulated according to cancer progression (NCF→CAF-PT→CAF-LM; fold change Log2 normalized expression>1.5 in each step). Prediction Analysis of Microarrays was applied to obtain a 25-gene signature that better characterizes each fibroblast class. The signature is able to classify patients carrying primary tumors according to prognosis. This fact was exploited to obtain a 19-gene signature (from the 277 deregulated probes) predicting recurrence with high accuracy in stage II/III colorectal cancer patients. Signature validation has been carried out in two independent datasets and in a meta-cohort of 336 stage II/III patients. Since the 25-gene signature was obtained regardless of gene expression data of tumor specimens or patient’s clinical data, the prognostic power of this signature provides strong evidence of the link between the tumor stroma and cancer progression. Furthermore, the 19-gene signature was able to identify low-risk patients with very high accuracy, especially relevant for those high-risk stage-II patients. We hybridised fibroblast RNA in Affymetrix GeneChip 1.0 st arrays

ORGANISM(S): Homo sapiens

SUBMITTER: david mollevi 

PROVIDER: E-GEOD-46824 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress