Single-cell Omics in Liver Cancer

Posted by beauty33 on March 31st, 2022

Liver cancer is the condition that cells grow out of control in the liver, which could be divided into two types. It\'s called primary liver cancer if it primarily happens in the liver, and if the cancer cells spread to the liver from a primary cancer spot somewhere else in the body, it would be secondary liver cancer. In the United States, about 35,000 men and women get liver cancer each year with 27,000 deaths, and the number has been rising for decades.

To develop possible therapies for the second most lethal cancer worldwide, researchers focus on understanding the tumor microenvironment (TME), in which liver cancer cells, immune cells, stromal cells, and many other cell types form an ecosystem. Understanding TME used to be a challenging task because cellular compositions and their dynamic intercellular interactions in this ecosystem are so complex. But continuous advances in single-cell techniques allow profiling multiple omics status and spatial information at the single-cell level, helping reveal the phenotypes and functionalities of disease-specific cell populations more comprehensively.

Single-cell Technologies

 

Single-cell technologies are increasingly developed and applied as important tools for biological analysis. Compared to conventional methods performing average measurements on bulk populations of cells, single-cell measurements on individual cells reveal complex cell interactions and unmask cell heterogeneity in the liver tissues. Single-cell sequencing, isolation, and indexing allow profiling the liver cancer microenvironment from different cellular scales with extremely high dimensions. Moreover, single-cell multi-omics methods, including genomic, transcriptomic, proteomic, and spatial information, have also been developed to simultaneously detect different omics of single cells.

Single-cell Omics in Liver Cancer

Single-cell data has been widely used to discover biomarkers for the diagnosis and prognosis prediction of liver cancer, as well as to identify new treatable targets and develop novel cancer immunotherapies. Single-cell omics can identify gene variations, tumor heterogeneity, and drug resistance, providing hints for the early diagnosis and individualized treatment of liver cancer. For instance, flow cytometry (FCM), one of the most widely used single-cell labeling and sorting techniques, has been applied to obtain data of single-cell omics in cancer biomarker tests, which contributes to identifying treatment-resistant cells in a cell population.

Original research published in the International Journal of General Medicine uses single-cell sequencing data to identify novel prognostic markers for hepatocellular carcinoma (HCC), the main histological subtype of liver cancer and a common malignancy featured with poor prognosis and high fatality rate. Single-cell sequencing technology based on single omics is a new technology that can observe characteristics of cells at a single-cell resolution, so this research team applies it for high-throughput sequencing analysis of genome, transcriptome, and epigenome, to uncover some key information that use to be ignored by conventional analysis. Single-cell data in this study help display the difference between homologous normal samples and tumor samples, reveal cellular interactions between different liver cells, analyze the key nodes where liver cells transform into liver cancer cells, and verify that deletion of these node genes is related to the occurrence and development of HCC.

Except for dissecting tumor microenvironments and describing the evolution of cancer cells in tumorigenesis and drug resistance, single-cell omics for liver cancer can also contribute to exploring cancer immunotherapies. Single-cell RNA sequencing and T-cell receptor (TCR) sequencing platforms have been integrated to improve the efficacy of promising immune checkpoint blockade (ICB) therapies and track dynamical T cell responses. For example, researchers found that the T cell landscape with the information of paired TCR α and β chains in liver cancers can disclose the transition route of exhausted CD8+ T cells in HCC, and they further noticed that a subset of CD8+ T cells with intermediate levels of PDCD1 and TIGIT could be the target cells for liver cancer immunotherapies.

Conclusion

Single-cell omics or multi-omics techniques are of great significance for liver cancer biology and immunology. These innovative single-cell omics technologies would be indispensable in studying basic and clinical liver cancer problems and exert great influence in the diagnosis, prognosis, and treatment of liver cancer and other diseases.

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beauty33
Joined: July 10th, 2017
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