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

Abstract

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.

An Overview on Single-Cell Technology for Hepatocellular Carcinoma Diagnosis

“…In addition, a hypoxic signature (14 genes of gene set) exhibited by subgroups common in numerous cell lines was identified, which can be related to drug-resistant mechanisms in cell lines. Thus, the results comprehensively provide a better understanding of the molecular mechanism behind the metastasis capacity of HCC, which will guide researchers towards the development of an efficient prognosis for HCC [52].…”

“…scATAC-seq recently has emerged as a powerful approach as it enabled characterization of gene regulatory activities in HCC. The breakthrough came when chromatin accessibility profiling helped in analyzing transcription regulation (the interaction between cis-acting DNA elements with transcription factor) [52]. Cumulatively, the technique provides a significant reference for the HCC analyses and prognosis.…”