Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer.

Wang, Fei; Long, Jie; Li, Liang; Wu, Zi-Xin; Da, Tian-Tian; Wang, Xiao-Qing; Huang, Chuan; Jiang, Yi-Hua et al. · Sci Adv · 2023

basic_science · Level V

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Abstract

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45<sup>-</sup> nonimmune cells and 196,473 CD45<sup>+</sup> immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. <i>F3</i><sup>+</sup> fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, <i>MCAM</i><sup>+</sup> fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.

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