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


ABSTRACT: 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 malignant 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.

SUBMITTER: Wang S 

PROVIDER: S-EPMC8850337 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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

Wang Shanshan S   Xie Jiarui J   Zou Xuanxuan X   Pan Taotao T   Yu Qichao Q   Zhuang Zhenkun Z   Zhong Yu Y   Zhao Xin X   Wang Zifei Z   Li Rui R   Lei Ying Y   Yin Jianhua J   Yuan Yue Y   Wei Xiaoyu X   Liu Longqi L   Liu Shiping S   Yang Huanming H   Wu Liang L  

iScience 20220202 3


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 identifie  ...[more]

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