Single-cell Multi-omics reveal heterogeneity and metastasis potential in different liver cancer cell lines

Hepatocellular carcinoma (HCC) is a malignant neo-plasm with a high recurrence and metastatic rate, accounted for poor prognosis. Commonly existed heterogeneity is concerned with neoplasia, cancer progression, therapeutic resistance and metastasis is the principal cause of cancer lethality. As development of multi-omics methods in single-cell technology provides multi-faceted insight into disease processes in the era of precision medicine. Here, we interrogated single-cell transcriptomes, proteomes and epigenetic information, revealing metastasis potential heterogeneity in 5 HCC cell lines across different metastasis capacity. We confirmed that higher mesenchymal (M) status but not proliferation rate was associated with stronger metastasis ability of cell lines. Besides, we identified a subgroup being common in several cell lines, showing a higher hypoxic signature. A gene set involving 14 genes were chosen to represent the hypoxia state, much consistent than previous reported gene set, and showed worse prognosis association in TCGA data. This hypoxic subgroup prefers glycolysis metabolism than OXPO, and showed non-cycling, quiescent state which could be resistant to many proliferation-targeting drugs. Our results provide a comprehensive understanding of characteristic associated with metastasis capacity of HCC cell line, which will guide the metastasis mechanism study of HCC.