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

nonimmune cells and 196,473 CD45
+
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.
F3
+
fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However,
MCAM
+
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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References
54
[1]
Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

Hyuna Sung, Jacques Ferlay, Rebecca L. Siegel et al.

CA: A Cancer Journal for Clinicians 10.3322/caac.21660
[2]
Cancer statistics, 2020

Rebecca L. Siegel, Kimberly D. Miller, Ahmedin Jemal

CA: A Cancer Journal for Clinicians 10.3322/caac.21590
[17]
W. Wang, Y. Zhong, Z. Zhuang, J. Xie, Y. Lu, C. Huang, Y. Sun, L. Wu, J. Yin, H. Yu, Z. Jiang, S. Wang, C. Wang, Y. Zhang, Y. Huang, C. Han, Z. Zhong, J. Hu, Y. Ouyang, H. Liu, M. Yu, X. Wei, D. Chen, L. Huang, Y. Hou, Z. Lin, S. Liu, F. Ling, X. Yao, Multiregion single-cell sequencing reveals the transcriptional landscape of the immune microenvironment of colorectal cancer. Clin. Transl. Med. 11, e253 (2021). 10.1002/ctm2.253
[19]
Single-cell dissection of transcriptional heterogeneity in human colon tumors

Piero Dalerba, Tomer Kalisky, Debashis Sahoo et al.

Nature Biotechnology 10.1038/nbt.2038
[21]
Myeloid-derived suppressor cells as regulators of the immune system

Dmitry I. Gabrilovich, Srinivas Nagaraj

Nature Reviews Immunology 10.1038/nri2506
[22]
A pan-cancer single-cell transcriptional atlas of tumor infiltrating myeloid cells

Sijin Cheng, Ziyi Li, Ranran Gao et al.

Cell 10.1016/j.cell.2021.01.010
[24]
Meta-analysis of tumor- and T cell-intrinsic mechanisms of sensitization to checkpoint inhibition

Kevin Litchfield, James L. Reading, Clare Puttick et al.

Cell 10.1016/j.cell.2021.01.002
[26]
Single-cell analyses reveal key immune cell subsets associated with response to PD-L1 blockade in triple-negative breast cancer

Yuanyuan Zhang, Hongyan Chen, Hongnan Mo et al.

Cancer Cell 10.1016/j.ccell.2021.09.010
[27]
Single-Cell Transcriptomic Analysis of Primary and Metastatic Tumor Ecosystems in Head and Neck Cancer

Sidharth V. Puram, Itay Tirosh, Anuraag S. Parikh et al.

Cell 10.1016/j.cell.2017.10.044
[29]
Activation of ERBB2 Signaling Causes Resistance to the EGFR-Directed Therapeutic Antibody Cetuximab

Kimio Yonesaka, Kreshnik Zejnullahu, Isamu Okamoto et al.

Science Translational Medicine 10.1126/scitranslmed.3002442
[30]
The Canonical Notch Signaling Pathway: Unfolding the Activation Mechanism

Raphael Kopan, Ma. Xenia G. Ilagan

Cell 10.1016/j.cell.2009.03.045
[36]
Targeting CXCL12 from FAP-expressing carcinoma-associated fibroblasts synergizes with anti–PD-L1 immunotherapy in pancreatic cancer

Christine Feig, James O. Jones, Matthew Kraman et al.

Proceedings of the National Academy of Sciences 10.1073/pnas.1320318110
[37]
A framework for advancing our understanding of cancer-associated fibroblasts

Erik Sahai, Igor Astsaturov, Edna Cukierman et al.

Nature Reviews Cancer 10.1038/s41568-019-0238-1
[44]
B cells and tertiary lymphoid structures promote immunotherapy response

Beth A. Helmink, Sangeetha M. Reddy, Jianjun Gao et al.

Nature 10.1038/s41586-019-1922-8
[50]
GSVA: gene set variation analysis for microarray and RNA-Seq data

Sonja Hänzelmann, Robert Castelo, Justin Guinney

BMC Bioinformatics 10.1186/1471-2105-14-7

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Details
Published
Jun 16, 2023
Vol/Issue
9(24)
Authors
Cite This Article
Fei Wang, Jie Long, Liang Li, et al. (2023). Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer. Science Advances, 9(24). https://doi.org/10.1126/sciadv.adf5464
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