Molecular landscape of colorectal cancer liver metastasis: Tumor microenvironment heterogeneity and driver inference

Liver metastasis of colorectal cancer (CRC) is the main cause of death for colorectal cancer. Recent studies have shown that, chromosomal instability (CIN) and the tumor microenvironment (TME) play critical roles in the process of liver metastasis in CRC, influencing both prognosis and therapeutic outcomes. The immune cells in the TME, especially the polarization of macrophages, which regulates immune suppression and extracellular matrix (ECM) remodeling, becomes a key driving factor for colorectal cancer liver metastasis. CIN enhances the plasticity of the tumor genome, activates metastasis-related pathways, and remodels the liver microenvironment, becoming an important driving force for colorectal cancer liver metastasis. This comprehensive review synthesizes the epidemiological researches of CRC, the impacts of chromosomal instability on liver metastasis and the mechanisms by which tumor microenvironment contributes to metastasis. It then summarizes the genes and related pathways that play important roles in TME and CIN processes, and explores their connections with colorectal cancer liver metastasis (CRLM). Finally, based on the above studies, the clinical significance in prognosis and treatment was discussed, potential targeted points with pertinence were proposed, and combined with the existing drug research, the feasibility of the conclusions was further demonstrated.