Integrated analysis of colorectal cancer metastasis identifies characteristics of tumor cell during metastasis.

Background: Metastasis is the main cause of death in colorectal cancer (CRC). Metastasis is a sequential and dynamic process, but the development of tumor cells during this process is unclear. In this study, we aimed to reveal characteristics of tumor cell subset during CRC metastasis.

Methods: Single-cell RNA sequence CRC data of normal epithelium, non-metastatic primary tumor, metastatic primary tumor, and liver metastases from gene expression omnibus (GEO) dataset were analyzed to reveal characteristics of CRC metastasis. Primary tumor tissues of three non-metastatic CRC and three metastatic CRC patients from Union Hospital of Tongji Medical College (Wuhan, China) were used to verify the characteristics of CRC metastasis.

Results: We identified a metastasis-related cancer cell subset EP1, which was characterized with a high expression of KRT17, LAMC2, EMP1, and PLAC8. EP1 had an enhanced cell-cell interaction, which interacted with SPP⁺ macrophages and drove them toward anti-inflammatory and immunosuppressive phenotype. Dynamic changes in genes and TF regulons during the metastasis were also revealed.

Conclusions: This study advanced our understanding of the development of tumor cells during CRC metastasis and further identified metastasis-related subset and potential therapeutic targets for the treatment and prevention of CRC metastasis.