Identification and validation of biomarkers related to mitophagy in chronic obstructive pulmonary disease

Chen,Jie; Zhang,Xiaofeng; Sun,Gengyun

doi:10.3892/mmr.2025.13458

Identification and validation of biomarkers related to mitophagy in chronic obstructive pulmonary disease

Authors:
- Jie Chen
- Xiaofeng Zhang
- Gengyun Sun
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Affiliations: Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China, Department of General Medicine, The Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230601, P.R. China
Published online on: February 11, 2025 https://doi.org/10.3892/mmr.2025.13458
Article Number: 93
Copyright: © Chen et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Mitophagy plays significant roles in chronic obstructive pulmonary disease (COPD). The present study aimed to screen and validate mitophagy‑related genes in COPD by using bioinformatic analysis and experimental validation. The original data were downloaded from Gene Expression Omnibus datasets and 29 mitophagy‑related genes sets were acquired from the Molecular Signatures Database. The differentially expressed mitophagy‑related genes (DEMRGs) were screened using the Wilcoxon test. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were conducted for the identification of DEMRGs. In addition, clustering analysis was used to assess the differential expression characteristics of DEMRGs in patients with COPD. Least absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify signature genes with COPD diagnostic significance; these genes were validated using the test dataset. In addition, the degree of infiltration of 28 immune cells in COPD and control samples was assessed. Finally, cigarette smoke extract (CSE)‑treated bronchial epithelial cells were employed to verify the role of signature genes in regulating mitophagy in vitro using molecular biology approaches. A total of 14 DEMRGs were identified, which were mainly involved in mitophagy‑related processes and pathways. Clustering analysis indicated the expression levels of 14 DEMRGs except for microtubule‑associated protein 1 light chain‑3β, which was significantly different. Moreover, combination with LASSO, receiver operating characteristic curve and the validation dataset resulted in the identification of the mitochondrial transcription termination factor 3 (MTERF3). The infiltrating abundance of the majority of the immune cells was higher in COPD samples than that noted in the control samples; MTERF3 demonstrated the optimal correlation with macrophages, myeloid‑derived suppressor cells, regulatory T cells and activated cluster of differentiation 8 T cells. Further analysis revealed that MTERF3 expression was increased in CSE‑treated 16HBE cells and knockdown of MTERF3 expression promoted mitophagy. These findings provide novel insights into the role of mitophagy in COPD and identify novel targets for COPD diagnosis and treatment.

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