Comparison of the tumor microenvironment between the primary site of colorectal cancer and liver metastases.

Surgical resection is effective for colorectal liver metastasis (CRLM), however, the molecular pathological mechanisms of them are not well understood. We hypothesized that the activity of tumors is altered by changes in the tumor microenvironment between colorectal cancer liver metastases and primary tumors. Tumor-associated macrophages (TAMs) have been reported as key components of the tumor microenvironment that regulate tumor activity in colorectal cancer. In this study, we performed RNA sequencing using FFPE tissue samples to screen for differentially expressed TAM-related genes between primary tumors and metastatic sites in colorectal cancer, aiming to identify the important factors involved in regulating tumor activity.We focused several TAM-related genes that showed differential expression between primary tumors and liver metastases in colorectal cancer. To confirm the RNA sequencing data, we conducted further validation using RNAscope in situ hybridization. As a result, we identified chemokine CCL1, a chemotactic factor for a ligand of Chemokine C-C motif receptor 8 (CCR8), as the gene with the most significant difference between the primary site and liver metastatic site of CRC. This gene was chosen as the focus for further investigation. we revealed the tumor-promoting role of the CCL1-CCR8 axis in enhancing cell motility through AKT signaling in Colorectal cancer, and furthermore, CCL1 expression in TAM at the liver metastatic site was lower compared to the primary site by histological analysis. These findings offer novel insights into CRLM and underscore the significance of surgical intervention.