2.1. Patients’ and Tissue Selection

Frozen samples from primary tumors obtained from CRC patients treated at Gustave Roussy cancer center and European Hospital Georges Pompidou were analyzed. Potentially resectable disease was defined according to metastatic site, tumor response to systemic chemotherapy and possibility of achieving a macroscopic resection with curative intent. Unresectable disease included a definitively unresectable metastatic disease, or presenting a progression after at least one line of systemic therapy enrolled in the MOSCATO-01 [26] ({"type":"clinical-trial","attrs":{"text":"NCT01566019","term_id":"NCT01566019"}}NCT01566019), a clinical trial aiming to evaluate the clinical benefit of targeted therapy guided by high-throughput genomic profiling.

Samples were prospectively collected and archived in both Centers during the study period and subsequently analyzed at Gustave Roussy Cancer Campus, Villejuif, France. The tumor tissue with highest cellularity on frozen sections was selected by the local pathologist. Tumor cellularity exceeding 30% was required for both primary tumor and metastatic tissues. Study data were collected and managed using REDCap electronic data capture tools hosted at Gustave Roussy Cancer Campus [27,28].

The surgical specimens were classified according to the TNM Classification (8th edition UICC/AJCC—2017). Clinico-pathological characteristics as well as the corresponding formalin-fixed paraffin-embedded (FFPE) tissue were collected for further analysis. Patients presenting a lack of data or specimen to correlate clinical data and gene expression profile, or presenting with co-malignancies, were excluded.

A specific written consent was obtained from all included patients. Dataset and specimens were irreversibly anonymized and researchers were blinded to the clinical and transcriptomic data during the analysis phase. The study was performed according to the recommendations of the local ethics committee of Gustave Roussy Cancer Campus, granted by Local Authorities, and was conducted in accordance with the Declaration of Helsinki.