Comprehensive analysis of spatial architecture in primary liver cancer.
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IF: 14.957
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Cited by: 70
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Abstract

Heterogeneity is the major challenge for cancer prevention and therapy. Here, we first constructed high-resolution spatial transcriptomes of primary liver cancers (PLCs) containing 84,823 spots within 21 tissues from seven patients. The progressive comparison of spatial tumor microenvironment (TME) characteristics from nontumor to leading-edge to tumor regions revealed that the tumor capsule potentially affects intratumor spatial cluster continuity, transcriptome diversity, and immune cell infiltration. Locally, we found that the bidirectional ligand-receptor interactions at the 100-μm-wide cluster-cluster boundary contribute to maintaining intratumor architecture and the PROM1+ and CD47+ cancer stem cell niches are related to TME remodeling and tumor metastasis. Last, we proposed a TLS-50 signature to accurately locate tertiary lymphoid structures (TLSs) spatially and unveiled that the distinct composition of TLSs is shaped by their distance to tumor cells. Our study provides previous unknown insights into the diverse tumor ecosystem of PLCs and has potential benefits for cancer intervention.

Keywords

Spatial Transcriptomics
HDST
MERFISH
CODEX
seqFISH+
Seurat

Authors

Wu, Rui
Guo, Wenbo
Qiu, Xinyao
Wang, Shicheng
Sui, Chengjun
Lian, Qiuyu
Wu, Jianmin
Shan, Yiran
Yang, Zhao
Yang, Shuai
Wu, Tong
Wang, Kaiting
Zhu, Yanjing
Wang, Shan
Liu, Changyi
Zhang, Yangqianwen
Zheng, Bo
Li, Zhixuan
Zhang, Yani
Shen, Siyun
Zhao, Yan
Wang, Wenwen
Bao, Jinxia
Hu, Ji
Wu, Xuan
Jiang, Xiaoqing
Wang, Hongyang
Gu, Jin
Chen, Lei

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