Fu Haoyu, Lu Xiaohuan, Ji Tiantian, Wang Liping, Wang Guobin, Wang Lin, Wang Zheng
Department of Gastrointestinal Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
Research Center for Tissue Engineering and Regenerative Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P. R. China.
Gastroenterol Rep (Oxf). 2024 May 30;12:goae055. doi: 10.1093/gastro/goae055. eCollection 2024.
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.
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.
We identified a metastasis-related cancer cell subset EP1, which was characterized with a high expression of , , , and . EP1 had an enhanced cell-cell interaction, which interacted with macrophages and drove them toward anti-inflammatory and immunosuppressive phenotype. Dynamic changes in genes and TF regulons during the metastasis were also revealed.
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.
转移是结直肠癌（CRC）患者死亡的主要原因。转移是一个连续且动态的过程，但在此过程中肿瘤细胞的发展尚不清楚。在本研究中，我们旨在揭示CRC转移过程中肿瘤细胞亚群的特征。
分析来自基因表达综合数据库（GEO）数据集的正常上皮、非转移性原发性肿瘤、转移性原发性肿瘤和肝转移灶的单细胞RNA序列CRC数据，以揭示CRC转移的特征。使用来自华中科技大学同济医学院附属协和医院（中国武汉）的3例非转移性CRC患者和3例转移性CRC患者的原发性肿瘤组织来验证CRC转移的特征。
我们鉴定出一个与转移相关的癌细胞亚群EP1，其特征是高表达 、 、 和 。EP1具有增强的细胞间相互作用，它与 巨噬细胞相互作用并促使它们向抗炎和免疫抑制表型转变。我们还揭示了转移过程中基因和转录因子调控子的动态变化。
本研究增进了我们对CRC转移过程中肿瘤细胞发展的理解，并进一步鉴定出与转移相关的亚群以及用于治疗和预防CRC转移的潜在治疗靶点。
