Single-cell multiomics reveals heterogeneous cell states linked to metastatic potential in liver cancer cell lines

Hepatocellular carcinoma (HCC) is the most common liver cancer with a high rate of metastasis. However, the molecular mechanisms that drive metastasis remain unclear. We combined single-cell transcriptomic, proteomic, and chromatin accessibility data to investigate how heterogeneous phenotypes contribute to metastatic potential in five HCC cell lines. We confirmed that the prevalence of a mesenchymal state and levels of cell proliferation are linked to the metastatic potential. We also identified a rare hypoxic subtype that has a higher capacity for glycolysis and exhibits dormant, invasive, and ma::gnant characteristics. This subtype has increased metastatic potential. We further identified a robust 14-gene panel representing this hypoxia signature and this hypoxia signature could serve as a prognostic index. Our data provide a valuable data resource, facilitate a deeper understanding of metastatic mechanisms, and may help diagnosis of metastatic potential in individual patients, thus supporting personalized medicine.

Automated summary

This study investigates the molecular mechanisms underlying metastasis in hepatocellular carcinoma (HCC) using single-cell transcriptomic, proteomic, and chromatin accessibility data. The researchers found that the prevalence of a mesenchymal state and levels of cell proliferation are linked to metastatic potential in HCC cell lines. They also identified a rare hypoxic subtype with increased glycolysis capacity and higher metastatic potential. Furthermore, they identified a 14-gene panel representing the hypoxia signature, which could serve as a prognostic index.