Association of Lung Tissue MicroRNA Expression with Quantitative Emphysema in COPD: An Exploratory Transcriptomic Analysis.
- 1Division of Pulmonology, Department of Internal Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.
- 2Department of Laboratory Medicine, Kosin University Gospel Hospital, Kosin University College of Medicine, Busan, Republic of Korea.
Abstract
Background
MicroRNAs (miRNAs) may participate in biological pathways relevant to emphysema, but their associations with quantitative emphysema in human lung tissue remain uncertain.Methods
We analyzed lung tissue miRNA expression and clinical phenotypes from 117 patients with COPD/emphysema in GSE201121. After expression filtering, 839 miRNA loci were evaluated for association with percent emphysema (quantitative CT-derived percent low-attenuation area below -950 HU) using linear regression adjusted for age and sex with HC3 heteroskedasticity-robust standard errors. Multiple testing was controlled using the Benjamini-Hochberg false discovery rate (BH-FDR). Significant loci were collapsed to unique mature miRNAs. Secondary analyses examined associations with FEV₁ % predicted, FEV₁/FVC, and DLCO. Sensitivity analyses excluded influential observations, used log-transformed percent emphysema, and evaluated former smokers with adjustment for pack-years. Experimentally validated miRNA-target interactions were queried using multiMiR, followed by Gene Ontology Biological Process enrichment.Results
Fourteen miRNAs were associated with percent emphysema at BH-FDR <0.05. Eight miRNAs showed positive associations with emphysema (miR-144-5p, miR-190a, miR-20b-5p, miR-451a, miR-3912, miR-15a-5p, miR-202-5p, and miR-4497), whereas six showed negative associations (miR-489, miR-181b-5p, miR-378a-5p, miR-3614-5p, miR-197-3p, and miR-877-3p). Associations with lung function were consistent with the emphysema findings across all 14 miRNAs. After phenotype-specific BH-FDR correction, 12 miRNAs were associated with FEV₁ % predicted, 12 with FEV₁/FVC, and 8 with DLCO. All 14 associations retained their direction and significance across sensitivity analyses. Enrichment analyses of experimentally supported targets identified processes related to miRNA regulation, apoptosis, hypoxia/oxygen responses, cell-cycle regulation, and vasculature development.Conclusion
Lung-tissue expression of 14 mature miRNAs was associated with percent emphysema and lung function in COPD, while target-enrichment findings based on experimentally supported interaction databases were exploratory and require independent and functional validation.
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BibTeX
@article{kim2026association,
title = {{Association of Lung Tissue MicroRNA Expression with Quantitative Emphysema in COPD: An Exploratory Transcriptomic Analysis.}},
author = {Taeyun Kim and Hyunji Choi and Chul-Ho Oak and Taehwa Kim and Tae Won Jang},
journal = {International journal of chronic obstructive pulmonary disease},
year = {2026},
month = oct,
doi = {10.2147/copd.s653811},
url = {https://europepmc.org/article/MED/42948330},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Association of Lung Tissue MicroRNA Expression with Quantitative Emphysema in COPD: An Exploratory Transcriptomic Analysis.
AU - Taeyun Kim
AU - Hyunji Choi
AU - Chul-Ho Oak
AU - Taehwa Kim
AU - Tae Won Jang
PY - 2026
DA - 2026/10/23
JO - International journal of chronic obstructive pulmonary disease
DO - 10.2147/copd.s653811
UR - https://europepmc.org/article/MED/42948330
AB - Background MicroRNAs (miRNAs) may participate in biological pathways relevant to emphysema, but their associations with quantitative emphysema in human lung tissue remain uncertain.Methods We analyzed lung tissue miRNA expression and clinical phenotypes from 117 patients with COPD/emphysema in GSE201121. After expression filtering, 839 miRNA loci were evaluated for association with percent emphysema (quantitative CT-derived percent low-attenuation area below -950 HU) using linear regression adjusted for age and sex with HC3 heteroskedasticity-robust standard errors. Multiple testing was controlled using the Benjamini-Hochberg false discovery rate (BH-FDR). Significant loci were collapsed to unique mature miRNAs. Secondary analyses examined associations with FEV₁ % predicted, FEV₁/FVC, and DLCO. Sensitivity analyses excluded influential observations, used log-transformed percent emphysema, and evaluated former smokers with adjustment for pack-years. Experimentally validated miRNA-target interactions were queried using multiMiR, followed by Gene Ontology Biological Process enrichment.Results Fourteen miRNAs were associated with percent emphysema at BH-FDR <0.05. Eight miRNAs showed positive associations with emphysema (miR-144-5p, miR-190a, miR-20b-5p, miR-451a, miR-3912, miR-15a-5p, miR-202-5p, and miR-4497), whereas six showed negative associations (miR-489, miR-181b-5p, miR-378a-5p, miR-3614-5p, miR-197-3p, and miR-877-3p). Associations with lung function were consistent with the emphysema findings across all 14 miRNAs. After phenotype-specific BH-FDR correction, 12 miRNAs were associated with FEV₁ % predicted, 12 with FEV₁/FVC, and 8 with DLCO. All 14 associations retained their direction and significance across sensitivity analyses. Enrichment analyses of experimentally supported targets identified processes related to miRNA regulation, apoptosis, hypoxia/oxygen responses, cell-cycle regulation, and vasculature development.Conclusion Lung-tissue expression of 14 mature miRNAs was associated with percent emphysema and lung function in COPD, while target-enrichment findings based on experimentally supported interaction databases were exploratory and require independent and functional validation.
SN - 1176-9106
SN - 1178-2005
ER -