Liver metastasis or peritoneal metastasis: single-cell RNA sequencing reveals the organotropism in colorectal cancer is driven by distinct partial-EMT processes.

Liver and peritoneum are the most common metastatic organs in colorectal cancer. However, the mechanisms of metastatic organotropism remain unexplored. Here we used single-cell RNA-sequencing to reveal the intermediate EMT state of tumor cells from colorectal cancer liver metastasis (CRLM) and colorectal cancer peritoneum metastasis (CRPM). There was a significant heterogeneity in expression profiles across multiple cell types in the tumor microenvironment between two groups. Although both groups of tumor cells obtained the activation of EMT, they were in different partial-EMT (pEMT) states and expressed distinct pEMT markers. Tumor cells in CRLM group were more in an epithelial-biased pEMT state, while a higher proportion of cells in CRPM group was in a mesenchymal-biased pEMT state. In addition, we observed differentially infiltrated myeloid and fibroblast sub-clusters, rendering the peritoneal metastasis group a more prominent inflammatory stimulus. Our study provides a comprehensive resource at single-cell level for in-depth exploration of metastatic organotropism in CRC.