Single-cell and spatial architecture of primary liver cancer
Pei‐Yun Zhou, Cheng Zhou, Wei Gan, Zheng Tang, Bao‐Ye Sun, Jinlong Huang, Gao Liu, Wei‐Ren Liu, Meng‐Xin Tian, Xi‐Fei Jiang, Han Wang, Chenyang Tao, Yuan Fang, Wei‐Feng Qu, Run Huang, Gui‐Qi Zhu, Cheng Huang, Xiutao Fu, Zhen‐Bin Ding, Qiang Gao, Jian Zhou, Ying–Hong Shi, Yong Yi, Jia Fan, Shuang‐Jian Qiu
Abstract
Abstract 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.