Spatial‒temporal heterogeneities of liver cancer and the discovery of the invasive zone.

Solid tumours are intricate and highly heterogeneous ecosystems, which grow in and invade normal organs. Their progression is mediated by cancer cells' interaction with different cell types, such as immune cells, stromal cells and endothelial cells, and with the extracellular matrix. Owing to its high incidence, aggressive growth and resistance to local and systemic treatments, liver cancer has particularly high mortality rates worldwide. In recent decades, spatial heterogeneity has garnered significant attention as an unfavourable biological characteristic of the tumour microenvironment, prompting extensive research into its role in liver tumour development. Advances in spatial omics have facilitated the detailed spatial analysis of cell types, states and cell‒cell interactions, allowing a thorough understanding of the spatial and temporal heterogeneities of tumour microenvironment and informing the development of novel therapeutic approaches. This review illustrates the latest discovery of the invasive zone, and systematically introduced specific macroscopic spatial heterogeneities, pathological spatial heterogeneities and tumour microenvironment heterogeneities of liver cancer.