Single cell-spatial transcriptomics and bulk multi-omics analysis of heterogeneity and ecosystems in hepatocellular carcinoma.

Abstract

This study profiled global single cell-spatial-bulk transcriptome landscapes of hepatocellular carcinoma (HCC) ecosystem from six HCC cases and a non-carcinoma liver control donor. We discovered that intratumoral heterogeneity mainly derived from HCC cells diversity and pervaded the genome-transcriptome-proteome-metabolome network. HCC cells are the core driving force of taming tumor-associated macrophages (TAMs) with pro-tumorigenic phenotypes for favor its dominant growth. Remarkably, M1-types TAMs had been characterized by disturbance of metabolism, poor antigen-presentation and immune-killing abilities. Besides, we found simultaneous cirrhotic and HCC lesions in an individual patient shared common origin and displayed parallel clone evolution via driving disparate immune reprograms for better environmental adaptation. Moreover, endothelial cells exhibited phenotypically conserved but executed differential functions in a space-dependent manner. Further, the spatiotemporal traits of rapid recurrence niche genes were identified and validated by immunohistochemistry. Our data unravels the great significance of HCC cells in shaping vibrant tumor ecosystems corresponding to clinical scenarios.
© 2024. The Author(s).

Authors

Jiazhou Ye, Yan Lin, Zhiling Liao, Xing Gao, Cheng Lu, Lu Lu, Julu Huang, Xi Huang, Shilin Huang, Hongping Yu, Tao Bai, Jie Chen, Xiaobo Wang, Mingzhi Xie, Min Luo, Jinyan Zhang, Feixiang Wu, Guobin Wu, Liang Ma, Bangde Xiang, Lequn Li, Yongqiang Li, Xiaoling Luo, Rong Liang

Department of Digestive Oncology, Guangxi Medical University Cancer Hospital, Nanning, China. liangrong@gxmu.edu.cn.