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bioRxiv · 10.1101/2022.11.03.515124

Integrated analysis of single-cell transcriptome of liver cancer and cirrhosis reveals cell lineage similarity and prognostic-associated subpopulations

Tong, M.·Luo, S.·Gu, L.·Zhang, Z.·Liang, C.·Tian, J.·Huang, H.·Lin, Y.·Huang, J.
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Abstract

Background & AimsLiver cancer is one of the most leading causes of cancer deaths. Cirrhosis is an important risk factor for liver cancer, which is the result of over-fibrosis caused by diffuse and long-term liver damage. Despite extensive research, a systematic study for characterizing similarity between liver cancer and cirrhosis at single cell resolution is still lacking. MethodsWe established a data analysis framework to elucidate cell lineage similarity between liver cancer and cirrhosis to discover prognostic-associated subpopulations. We integrated single-cell transcriptome data from liver samples at normal, cirrhotic and cancer conditions, which totally contained 78,000 cells. Gene regulation analysis, cellular interactions and trajectory analysis were performed to characterize cirrhosis-like cell subpopulations. Bulk transcriptomes were used to discover prognostic-associated subpopulations. ResultsBy aligning cellular subpopulations across different samples, we found remarkable similarity between KNG1+ hepatocytes in cirrhosis and PGA5+ hepatocytes in HCC. Furthermore, gene regulation analysis and cellular interactions implicated E2F1, FOXA2, EGF, CDH and ANGPTL signaling in maintaining cirrhosis-like ecosystem. Strikingly, subpopulations with higher expression of cirrhosis-like signatures were associated with patients worse survival. ConclusionsWe revealed a previously unexplored cirrhosis-like ecosystem of liver cancer, which could provide novel biomarkers for therapeutic interventions in HCC. Core analysis modules in this study were integrated into a user-friendly toolkit, SIMscRNA(https://github.com/xmuhuanglab/SIM-scRNA), which could facilitate the exploration of similarity and heterogeneity between precancerous diseases and solid tumors.

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Tong, M., Luo, S., Gu, L., Zhang, Z., Liang, C., Tian, J., Huang, H., Lin, Y., Huang, J.. 2022-11-04. Integrated analysis of single-cell transcriptome of liver cancer and cirrhosis reveals cell lineage similarity and prognostic-associated subpopulations. https://doi.org/10.1101/2022.11.03.515124

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