Single-cell and spatial architecture of primary liver cancer

• Published in: Communications biology Vol. 6; no. 1; pp. 1181 - 17
• Main Authors: Zhou, Pei-Yun, Zhou, Cheng, Gan, Wei, Tang, Zheng, Sun, Bao-Ye, Huang, Jin-Long, Liu, Gao, Liu, Wei-Ren, Tian, Meng-Xin, Jiang, Xi-Fei, Wang, Han, Tao, Chen-Yang, Fang, Yuan, Qu, Wei-Feng, Huang, Run, Zhu, Gui-Qi, Huang, Cheng, Fu, Xiu-Tao, Ding, Zhen-Bin, Gao, Qiang, Zhou, Jian, Shi, Ying-Hong, Yi, Yong, Fan, Jia, Qiu, Shuang-Jian
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.11.2023; Nature Publishing Group; Nature Portfolio
• Subjects: 631/67/1504/1610/4029; 631/67/327; Bile Duct Neoplasms - genetics; Bile Ducts, Intrahepatic; Biology; Biomedical and Life Sciences; Carcinoma, Hepatocellular - pathology; Cholangiocarcinoma; Cholangiocarcinoma - genetics; Endothelial cells; Endothelial Cells - metabolism; Fibroblasts; Hepatocellular carcinoma; Heterogeneity; Humans; Life Sciences; Liver cancer; Liver Neoplasms - pathology; Lymphocytes T; Microenvironments; Phenotypes; Transcriptomics; Tumor Microenvironment - genetics; Tumors
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-023-05455-0

Primary liver cancer (PLC) poses a leading threat to human health, and its treatment options are limited. Meanwhile, the investigation of homogeneity and heterogeneity among PLCs remains challenging. Here, using single-cell RNA sequencing, spatial transcriptomic and bulk multi-omics, we elaborated a molecular architecture of 3 PLC types, namely hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and combined hepatocellular-cholangiocarcinoma (CHC). Taking a high-resolution perspective, our observations revealed that CHC cells exhibit internally discordant phenotypes, whereas ICC and HCC exhibit distinct tumor-specific features. Specifically, ICC was found to be the primary source of cancer-associated fibroblasts, while HCC exhibited disrupted metabolism and greater individual heterogeneity of T cells. We further revealed a diversity of intermediate-state cells residing in the tumor-peritumor junctional zone, including a congregation of CPE + intermediate-state endothelial cells (ECs), which harbored the molecular characteristics of tumor-associated ECs and normal ECs. This architecture offers insights into molecular characteristics of PLC microenvironment, and hints that the tumor-peritumor junctional zone could serve as a targeted region for precise therapeutical strategies. A comprehensive multi-omic, single-cell, and spatial analysis provides further insight into the major cell types present in three types of primary liver cancer.