In this study we aimed to explore the molecular landscape of hepatic metastases and adjacent tissue in order to delineate a potential molecular signature that may be predictive for clinical benefit of CRCLM resection. Consecutive patients who underwent CRCLM resection between 2008 and 2015 at RMC, and for whom pathological specimen was available were included in the study. Cases were divided into two cohorts based on the interval between resection of liver metastases and disease recurrence- patients with less than 12-month interval were defined as ×´poor prognosis×´ (PP) and patients with more than 12 months as ×´good prognosis×´ (GP). Clinical data was retrieved from the medical records. Proteomic analysis was performed on the pathological bio specimen and correlated to demographics and clinical outcomes. Fifty-eight patients were included in the study. 29 in the GP cohort and 29 in the PP cohort. Proteomic analysis of the two-cohort revealed 99 proteins that were 38 differentially expressed, about a third of them associate with the extracellular matrix (ECM) pathways as the matrix metalloproteinases (MMPs).