ORIGINAL RESEARCH article
Front. Immunol.
Sec. Cancer Immunity and Immunotherapy
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1585505
This article is part of the Research TopicIntegrative Multi-Omics Approaches for Predicting Immunotherapy Efficacy in Solid TumorsView all 6 articles
Integrated Multi-Omics Analysis and Experimental Investigation of Mitochondrial Dynamics-Related Genes: Molecular Subtypes, Immune Landscape, and Prognostic Implications in Lung Adenocarcinoma
Provisionally accepted
- 1The First Affiliated Hospital, University of South China, Hengyang, China
- 2Fujian Medical University, Fuzhou, Fujian Province, China
- 3Shaoyang University, Tangdukou, China
- 4Xiamen University, Xiamen, Fujian Province, China
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Background: Lung adenocarcinoma (LUAD) is a common and aggressive subtype of lung cancer associated with poor clinical outcomes. The role of mitochondrial dynamics (MD)-related genes in tumor progression and immune regulation remains poorly understood. Methods: Data from public databases were integrated, and subtypes were classified based on 23 MD-related genes. A five-gene prognostic model was constructed. Associations between the model and immune infiltration, tumor mutational burden (TMB), tumor stemness, and drug sensitivity were analyzed. The function of the key gene MTCH2 was validated through in vitro experiments. Results: Two distinct MD molecular subtypes were identified, exhibiting significant differences in prognosis and immune characteristics. A corresponding risk score model was established. Patients in the low-risk group showed better prognosis and enhanced immune activity, whereas the high-risk group displayed higher TMB and stemness scores. Drug sensitivity analysis revealed distinct responses to chemotherapeutic agents such as cisplatin and docetaxel between risk groups.Functional assays demonstrated that MTCH2 knockout significantly inhibited LUAD cell proliferation, migration, and invasion, and induced G0/G1 phase arrest, suggesting that MTCH2 may act as a potential adverse prognostic marker.MD-related genes exhibit strong prognostic and immune subtyping value. The proposed risk model holds clinical potential, and MTCH2 may serve as a promising target for precision therapy in LUAD.
Keywords: LUAD, mitochondrial dynamics, Prognostic model, Tumor Microenvironment, MTCH2
Received: 28 Feb 2025; Accepted: 12 May 2025.
Copyright: © 2025 Wu, Pan, Zeng, Pan, Yu, Lin, Zhang and Jiang. 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: Yiling Jiang, The First Affiliated Hospital, University of South China, Hengyang, China
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