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

整合分析结直肠癌转移过程识别肿瘤细胞转移特征

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作者:Haoyu Fu, Xiaohuan Lu, Tiantian Ji, Liping Wang, Guobin Wang, Lin Wang, Zheng Wang

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.

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.

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.

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