AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO026090107
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ORIGINAL RESEARCH ARTICLE

Translocator protein drives hepatocellular carcinoma progression through suppression of ferroptosis and apoptosis

Jingpu Shi1 ,  Zhilei Zhang2 ,  Yuming Jia2 ,  Chao Wang2 ,  Lantao Wang3* ,  Xin Wang3*
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1 Department of Anesthesiology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
2 Department of Hepatobiliary Surgery, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
3 Department of Emergency, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, China
EJMO, 026090107 https://doi.org/10.36922/EJMO026090107
Received: 1 March 2026 | Revised: 1 April 2026 | Accepted: 29 April 2026 | Published online: 22 May 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Introduction: Hepatocellular carcinoma (HCC) is an aggressive, primary liver cancer with dismal survival rates and a scarcity of effective treatments. Ferroptosis, a regulated, iron-dependent cell death mechanism mediated by lipid peroxidation, has emerged as a critical contributor to tumor progression. However, the interplay between ferroptosis and apoptosis in HCC remains incompletely understood. The translocator protein (TSPO) is implicated in tumor progression; however, its specific contribution to HCC pathogenesis remains to be fully elucidated.

Objective: To explore the expression landscape, clinical relevance, and functional significance of TSPO in HCC, with a particular focus on its modulation of ferroptosis and apoptosis.

Methods: Ferroptosis-related differentially expressed genes (DEGs) were identified from GEO and FerrDb databases and analyzed using functional enrichment and protein–protein interaction networks. The Cancer Genome Atlas Liver Hepatocellular Carcinoma data were utilized to assess TSPO expression, correlation with clinical features, functional enrichment, and immune cell infiltration. In vitro experiments evaluated the effects of TSPO on HCC cell proliferation, ferroptosis and apoptosis markers, reactive oxygen species (ROS) levels, intracellular Fe2+, and lipid peroxidation.

Results: We identified 49 ferroptosis-related DEGs, which were predominantly enriched in pathways related to iron homeostasis, oxidative stress response, apoptosis, and mitochondrial function. TSPO expression was significantly upregulated in HCC tissues, correlating with poor overall survival (hazard ratio = 1.42, p < 0.05) and moderate diagnostic performance (area under the curve = 0.699). Functional assays showed that TSPO overexpression enhanced cell proliferation, elevated solute carrier family 7 member 11, solute carrier family 3 member 2, and glutathione peroxidase 4 levels, and reduced reactive oxygen species accumulation, intracellular Fe2+, and lipid peroxidation. Moreover, TSPO overexpression inhibited apoptosis by upregulating B-cell lymphoma 2 (Bcl-2) and downregulating Bcl-2-associated X protein and p53, with opposite effects observed upon TSPO knockdown.

Conclusion: Overall, TSPO drives HCC progression by inhibiting ferroptosis and apoptosis, underscoring its value as a prognostic indicator and potential therapeutic target.

Graphical abstract
Keywords
Translocator protein
Hepatocellular carcinoma
Ferroptosis
Apoptosis
Prognosis
Funding
None.
Conflict of interest
The authors declare they have no competing interests.
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Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
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