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ORIGINAL RESEARCH article

Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 | doi: 10.3389/fimmu.2024.1496886
This article is part of the Research Topic Immunological Precision Therapeutics: Integrating Multi-Omics Technologies and Comprehensive Approaches for Personalized Immune Intervention View all 22 articles

Integrating multi-omics techniques and in vitro experiments reveals that GLRX3 regulates the immune microenvironment and promotes hepatocellular carcinoma cell proliferation and invasion through iron metabolism pathways

Provisionally accepted
Yang Li Yang Li 1Yuan Chen Yuan Chen 1*Yang Zhang Yang Zhang 1*Yunsheng Fang Yunsheng Fang 2*Ling Wu Ling Wu 1*Ying Zhao Ying Zhao 1*Danqiong Wang Danqiong Wang 1*Xiaoyuan Qiao Xiaoyuan Qiao 3*
  • 1 Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
  • 2 Xi'an Jiaotong University, Xi'an, China
  • 3 Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China

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

    Background: Hepatocellular carcinoma (HCC) is a common malignancy worldwide, and its development is closely related to abnormalities in iron metabolism.This study aims to systematically analyze changes in iron metabolism in the tumor microenvironment of HCC using single-cell sequencing technology, and investigate the potential mechanisms by which iron metabolism regulation affects the survival of liver cancer patients.Single-cell sequencing data from hepatocellular carcinoma patients were obtained from the GEO database. By iron metabolism genomic scoring, we assessed differences in iron metabolism levels in hepatocellular carcinoma samples. By cell communication analysis as well as GO and KEGG enrichment analysis, we determined the functional role of iron metabolism in GLRX3 in HCC: Precision Targeting 2 different cell types. We used survival analysis and Kaplan-Meier curves to assess the impact of iron metabolism levels on patient prognosis. In addition, we identified and analyzed the expression profile of the GLRX3 gene, investigated its key regulatory role in iron metabolism, and validated its clinical value as a prognostic marker. Finally, we explored the effect of GLRX3 on hepatocellular carcinoma phenotype by in vitro experiments such as PCR, transwell, CCK8, and wound healing assay.Results: Bioinformatics results and experimental validation confirmed the dysregulation of iron metabolism in the development of hepatocellular carcinoma, revealing iron's regulatory influence across various cell types. Additionally, GLRX3 was identified as a key regulatory factor in iron metabolism, and the mechanism by which GLRX3 regulates tumor cell proliferation and immune evasion was determined. Furthermore, experiments verified GLRX3's role in facilitating tumor cell proliferation and invasion.This study highlights the critical role of iron metabolism in the progression of hepatocellular carcinoma, particularly the regulatory mechanism of the GLRX3 gene in tumor cell proliferation and immune evasion. Iron metabolism abnormalities are not only drivers of liver cancer development but also key indicators of patient prognosis.

    Keywords: iron metabolism, GLRX3，lmmunotherapy, precision medicine, Multi-omics analysis, lmmune Signatures, personalized therapy

    Received: 15 Sep 2024; Accepted: 06 Nov 2024.

    Copyright: © 2024 Li, Chen, Zhang, Fang, Wu, Zhao, Wang and Qiao. 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:
    Yuan Chen, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
    Yang Zhang, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
    Yunsheng Fang, Xi'an Jiaotong University, Xi'an, 710049, China
    Ling Wu, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
    Ying Zhao, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
    Danqiong Wang, Shanxi Bethune Hospital, Shanxi Medical University, Taiyuan, China
    Xiaoyuan Qiao, Shanxi Provincial Cancer Hospital, Taiyuan, Shanxi Province, China

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