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ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 15 - 2024 |
doi: 10.3389/fimmu.2024.1415435
This article is part of the Research Topic Single-Cell Sequencing of the Immune Microenvironment in Cancer View all 3 articles
HMGB2 Drives Tumor Progression and Shapes the Immunosuppressive Microenvironment in Hepatocellular Carcinoma: Insights from Multi-Omics Analysis
Provisionally accepted- 1 Department of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
- 2 Department of Ophthalmology, Second Xiangya Hospital, Central South University, Changsha, Hunan Province, China
- 3 Department of Radiation Oncology, Shanghai East Hospital Ji’an hospital, Ji'an, China
Background: Hepatocellular carcinoma (HCC) poses a significant health burden globally, with high mortality rates despite various treatment options. Immunotherapy, particularly immune-checkpoint inhibitors (ICIs), has shown promise, but resistance and metastasis remain major challenges. Understanding the intricacies of the tumor microenvironment (TME) is imperative for optimizing HCC management strategies and enhancing patient prognosis. Methods: This study employed a comprehensive approach integrating multi-omics approaches, including single-cell RNA sequencing (scRNA-seq), bulk RNA sequencing (Bulk RNA-seq), and validation in clinical samples using spatial transcriptomics (ST) and multiplex immunohistochemistry (mIHC). The analysis aimed to identify key factors influencing the immunosuppressive microenvironment associated with HCC metastasis and immunotherapy resistance. Results: The results revealed that HMGB2 is significantly upregulated in HCCTrans, a transitional subgroup associated with aggressive metastasis. Furthermore, HMGB2 expression positively correlates with an immunosuppressive microenvironment, particularly evident in exhausted T cells. Notably, HMGB2 expression correlated positively with immunosuppressive markers and poor prognosis in HCC patients across multiple cohorts. ST combined with mIHC validated the spatial expression patterns of HMGB2 within the TME, providing additional evidence of its role in HCC progression and immune evasion. Conclusion: HMGB2 emerges as a critical player of HCC progression, metastasis, and immunosuppression. Its elevated expression correlates with aggressive tumor behavior and poor patient outcomes, suggesting its potential as both a therapeutic target and a prognostic indicator in HCC management.
Keywords: Hepatocellular Carcinoma, HMGB2, Multi-omics approaches, Computational biology and bioinformatics, Tumor Microenvironment, Immunosuppression
Received: 10 Apr 2024; Accepted: 02 Aug 2024.
Copyright: © 2024 Chen, Meng and Xiang. 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:
Zuo-Lin Xiang, Department of Radiation Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China
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