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

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 (NCFCAF-PTCAF-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.

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