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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1502263

Biomarkers and potential therapeutic targets driving progression of non-alcoholic steatohepatitis to hepatocellular carcinoma predicted through transcriptomic analysis

Provisionally accepted
Fan Hui Fan Hui Rong Wang Rong Wang Bin Wen Bin Wen Jing Xiong Jing Xiong *
  • China Pharmaceutical University, Nanjing, China

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

    Background: Non-alcoholic steatohepatitis (NASH) is the most prevalent chronic liver condition globally, with potential progression to cirrhosis, and even hepatocellular carcinoma (HCC). The increasing prevalence of NASH underscores the urgent need for advanced diagnostic and therapeutic strategies. Despite its widespread impact, effective treatments to prevent the progression of NASH remain elusive, highlighting the critical importance of innovative molecular techniques in both the diagnosis and management of this disease.Methods: Six microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs).We identified 62 robust upregulated genes and 24 robust downregulated genes. These genes were undergone Gene Ontology enrichment analysis and further examination for expression correlation with NAS score. Molecular subtypes were generated using "ConsensusClusterPlus" on identified genes, which were further assessed for tumor stage relevance, expression differences in adjacent and tumor tissues, and impact on survival in TCGA liver cancer patients. Single-cell analysis was then used to explore the genes across different cell types and subgroups as well as cell-type interactions. The clinical utility of predicted core genes was highlighted through decision curve analysis, with emphasis on HCC prognosis. The GDSC database was used to evaluate the relationship between the predicted core genes and drug sensitivity, while the TIDE database was used to evaluate their relationship with immunotherapy.Results: Four core genes, TREM2, GDF15, TTC39A, and ANXA2, were identified as key to influencing HCC prognosis and therapy responsiveness, especially immune treatment efficacy in NASH-associated HCC.The core genes may act as critical biomarkers driving the progression of NASH to HCC. They are potential novel targets for the diagnosis and treatment of NASH progression, offering innovative perspectives for its clinical management.

    Keywords: non-alcoholic steatohepatitis, Triggering receptor expressed on myeloid cells 2, Annexin A2, growth/differentiation factor-15, tetratricopeptide repeat domain 39A, Hepatocellular Carcinoma, Bioinformatic analysis

    Received: 27 Sep 2024; Accepted: 11 Nov 2024.

    Copyright: © 2024 Hui, Wang, Wen and Xiong. 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: Jing Xiong, 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.