AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025180152
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ORIGINAL RESEARCH ARTICLE

Investigating the role of TIMM8B in lung adenocarcinoma: Expression patterns, prognostic value, and therapeutic implications

Zhuli Zheng1† ,  Libao Gong1† ,  Hongcheng Zhong2† ,  Bingjiang Huang1 ,  Yunyan Cong1 ,  Beilong Zhong2* ,  Zhihui Wang1*
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1 Department of Thoracic Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
2 Department of Thoracic Surgery, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, China
†These authors contributed equally to this work.
EJMO, 025180152 https://doi.org/10.36922/EJMO025180152
Received: 28 April 2025 | Revised: 1 June 2025 | Accepted: 24 June 2025 | Published online: 25 August 2025
© 2025 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: Translocase of inner mitochondrial membrane 8 homolog B (TIMM8B) is crucial for mitochondrial function, but its role in lung adenocarcinoma (LUAD) remains underexplored.

Objective: This study investigates TIMM8B expression patterns, prognostic value, and potential therapeutic implications in LUAD.

Methods: The expression and prognostic potential of TIMM8B in LUAD were analyzed using data from The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression, Gene Expression Omnibus, and Gene Expression Profiling Interactive Analysis 2, with survival analysis performed through Kaplan–Meier plotter. The prognostic value was validated using a LUAD tissue microarray and a nomogram. TIMM8B-related differentially expressed genes were identified using TCGA and LinkedOmics, and were functionally annotated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. Immunological features were assessed using TCGA data through the XCELL and tumor immune dysfunction and exclusion algorithms. Associations among TIMM8B, m6A modification, ferroptosis-related genes, and tumor genetic mutations were analyzed using TCGA data. Drug response correlations were explored using the Genomics of Drug Sensitivity in Cancer and Comparative Toxicogenomics databases. TIMM8B-depleted LUAD cell lines were analyzed using ribonucleic acid sequencing and subjected to cell cycle analysis.

Results: TIMM8B is overexpressed in multiple cancers, including LUAD. High TIMM8B expression correlates with poorer overall survival in LUAD. A nomogram incorporating TIMM8B and pathological tumor-node-metastasis stage showed reliable predictive performance. TIMM8B-related gene analyses suggest roles in cell adhesion, chromosome segregation, and critical cancer pathways. TIMM8B shapes an immunosuppressive tumor microenvironment in LUAD, affecting immune cell infiltration and immunotherapy response. Elevated TIMM8B expression is associated with TP53 mutations and chemotherapy resistance. Knockdown of TIMM8B in H1299 cells downregulates PD-L1, induces G1 phase arrest, and triggers a chemokine (C-C motif) ligand 2-mediated inflammatory response, highlighting roles in cell cycle regulation and inflammatory pathways.

Conclusion: These findings underscore TIMM8B’s multifaceted role in cancer progression and its potential as a prognostic marker and therapeutic target in LUAD.

Keywords
Translocase of inner mitochondrial membrane 8 homolog B
Prognosis
Immunotherapy
Inflammatory
Lung adenocarcinoma
Funding
This work was supported by the Science and Technology Project Grant of Zhuhai (grant number: 2220004000224).
Conflict of interest
The authors declare 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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