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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1455383

Integrated single-cell and bulk RNA sequencing reveals immune-related SPP1+ macrophages as a potential strategy for predicting the prognosis and treatment of liver fibrosis and hepatocellular carcinoma

Provisionally accepted
Bangjie Li Bangjie Li Jialiang Hu Jialiang Hu *Hanmei Xu Hanmei Xu *
  • China Pharmaceutical University, Nanjing, China

The final, formatted version of the article will be published soon.

    Background: Liver fibrosis is a pathological response to liver damage induced by multiple etiologies including NASH and CCl4, which may further lead to cirrhosis and hepatocellular carcinoma (HCC). Despite the increasing understanding of liver fibrosis and HCC, clinical prognosis and targeted therapy remain challenging.This study integrated single-cell sequencing analysis, bulk sequencing analysis, and mouse models to identify highly expressed genes, cell subsets, and signaling pathways associated with liver fibrosis and HCC. Clinical prediction models and prognostic genes were established and verified through machine learning, survival analysis, as well as the utilization of clinical data and tissue samples from HCC patients. The expression heterogeneity of the core prognostic gene, along with its correlation with the tumor microenvironment and prognostic outcomes, was analyzed through single-cell analysis and immune infiltration analysis. In addition, the cAMP database and molecular docking techniques were employed to screen potential small molecule drugs for the treatment of liver fibrosis and HCC.Result: We identified 40 pathogenic genes, 15 critical cell subsets (especially Macrophages), and regulatory signaling pathways related to cell adhesion and the actin cytoskeleton that promote the development of liver fibrosis and HCC. In addition, 7 specific prognostic genes (CCR7, COL3A1, FMNL2, HP, PFN1, SPP1 and TENM4) were identified and evaluated, and expression heterogeneity of core gene SPP1 and its positive correlation with immune infiltration and prognostic development were interpreted. Moreover, 6 potential small molecule drugs for the treatment of liver fibrosis and HCC were provided.The comprehensive investigation, based on a bioinformatics and mouse model strategy, may identify pathogenic genes, cell subsets, regulatory mechanisms, prognostic genes, and potential small molecule drugs, thereby providing valuable insights into the clinical prognosis and targeted treatment of liver fibrosis and HCC.

    Keywords: liver fibrosis, Hepatocellular Carcinoma, Prediction model, SPP1, Single cell sequencing

    Received: 26 Jun 2024; Accepted: 04 Nov 2024.

    Copyright: © 2024 Li, Hu and Xu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Jialiang Hu, China Pharmaceutical University, Nanjing, China
    Hanmei Xu, China Pharmaceutical University, Nanjing, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.