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ORIGINAL RESEARCH article

Front. Med.

Sec. Pulmonary Medicine

Volume 12 - 2025 | doi: 10.3389/fmed.2025.1612390

Identification and validation for biomarkers associated with mitochondrial metabolism in chronic obstructive pulmonary disease

Provisionally accepted
Wenjun  WangWenjun Wang1*Lanxiang  WuLanxiang Wu2Chao  OuyangChao Ouyang3Tao  HuangTao Huang1
  • 1State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China
  • 2Department of Neurology, the Second Affliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, China
  • 3Department of Respiratory Diseases, Nanchang People's Hospital, Nanchang,, Nanchang, Jiangxi Province, China

The final, formatted version of the article will be published soon.

Background: Chronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with no studies on the biological role of mitochondrial metabolism (MM). This study aimed to explore MM mechanisms in COPD using bioinformatics methods.The GSE57148 and GSE8581 were downloaded from GEO, and 1234 MM related genes (MM-RGs) were downloaded from literature. In GSE57148, differentially expressed genes (DEGs) were determined. The intersection of DEGs and MM-RGs was taken to obtain candidate genes. Proteinprotein interaction (PPI) network was used to obtained candidate key genes. Machine learning was employed to detect key genes. The biomarkers were identified through expression validation and receiver operating characteristic (ROC) curves. Subsequently, a nomogram was developed to forecast the likelihood of developing COPD. In addition, functional enrichment, immune infiltration, molecular regulatory network and drug prediction were carried out. Finaly, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry analysis were used to verify DEGs of lung tissues of COPD patients and controls.Results: Adenine phosphoribosyltransferase (APRT) and lecithin-cholesterol acyltransferase (LCAT) were identified as biomarkers. Subsequently, a nomogram was formulated utilizing 2 biomarkers, revealing their significant diagnostic potential. Pathways co-enriched by 2 biomarkers included ribosome, etc. Immune infiltration analysis showed that 15 types of immune cells were differential immune cells. APRT predicted a total of 30 miRNAs and LCAT predicted a total of 17 miRNAs. The APRT identified predicted a total of 178 transcription factors (TFs), the LCAT identified predicted a total of 86 TFs. TFs shared by both biomarkers include SPI1, CTCF and BCL3, etc. Finally, drug prediction analysis found a total of 114 target drugs for APRT and 156 target drugs for LCAT. The mRNA and protein expression of APRT and LCAT were significantly decreased in COPD patient lung tissues.APRT and LCAT were identified as biomarkers for COPD, this provides deeper understanding into the mechanisms behind COPD and identifies potential markers for early diagnosis and therapeutic intervention.

Keywords: chronic obstructive pulmonary disease, drug forecasting, mitochondrial metabolism, Immune infiltration, biomarkers

Received: 15 Apr 2025; Accepted: 05 Aug 2025.

Copyright: © 2025 Wang, Wu, Ouyang and Huang. 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: Wenjun Wang, State Key Laboratory of Respiratory Diseases, Guangzhou Medical University, Guangzhou, China

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