Interrogating subclonal heterogeneity of liver cancer with single-cell multi-omics analysis

Hepatocellular carcinomas (HCC) with multinodular morphology were typically polyclonal and exhibited extensive heterogeneity. We explored the multiple-layer heterogeneity of HCC utilizing single-cell multiomics sequencing together with multiregional sampling. We found that Confluent Multi-Nodular samples exhibit more heterogeneous immune landscapes characterized by increased transcriptome heterogeneity and more complex immune-related interactions compared to Single Nodular (SN) samples. We identified differential DNA methylation patterns among distinct tumor foci in a subset of liver cancer patients. Global DNA hypomethylation in cancer cells predominantly occurs in partially methylated domains. We predicted and validated two genes, GADD45A and SNHG6, as potential drivers of DNA hypomethylation. Lastly, we demonstrated that DNA methylation distance serves as a more robust metric than gene expression distance for reconstructing tumor evolutionary trajectories.

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Publication Details

Journal
Scientific Reports
Published
2025-11-07
DOI
https://doi.org/10.1038/s41598-025-24732-y
Citations
1
Primary Topic
Single-cell and spatial transcriptomics
Type
article
Field-Weighted Citation Impact
0.81

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article

Interrogating subclonal heterogeneity of liver cancer with single-cell multi-omics analysis

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Scientific Reports
Single-cell and spatial transcriptomics
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Interrogating subclonal heterogeneity of liver cancer with single-cell multi-omics analysis

Dandan Hu, Xiaoying Fan, En-Ze Deng, Yaojun Zhang, Longxi Li, Xiao‐Ou Zhang, Qingpei Huang, Dan Su, Xing Peng, Kai Tian, Liwen Zhang, Xiong Xiong, Zihua Su, Weiyuan Ma, Lei Chang, Yi Guo, Hongjian Qi
article en
1 citations

Abstract

Hepatocellular carcinomas (HCC) with multinodular morphology were typically polyclonal and exhibited extensive heterogeneity. We explored the multiple-layer heterogeneity of HCC utilizing single-cell multiomics sequencing together with multiregional sampling. We found that Confluent Multi-Nodular samples exhibit more heterogeneous immune landscapes characterized by increased transcriptome heterogeneity and more complex immune-related interactions compared to Single Nodular (SN) samples. We identified differential DNA methylation patterns among distinct tumor foci in a subset of liver cancer patients. Global DNA hypomethylation in cancer cells predominantly occurs in partially methylated domains. We predicted and validated two genes, GADD45A and SNHG6, as potential drivers of DNA hypomethylation. Lastly, we demonstrated that DNA methylation distance serves as a more robust metric than gene expression distance for reconstructing tumor evolutionary trajectories.

Scientific ReportsVol. 15(1)
Sun Yat-sen University (CN), Westlake University (CN), Guangzhou Experimental Station (CN), Sun Yat-sen University Cancer Center (CN), State Key Laboratory of Oncology in South China
Westlake University, National Natural Science Foundation of China
Openalex Percentile: Top 22%
Single-cell and spatial transcriptomics
0.81
DOIOpen Access PDFOpenAlex
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