Identification of Five Candidate Genes and Development of an Exploratory Diagnostic Nomogram for COPD Using Integrative Single-Cell and Bulk Transcriptomic Analyses.
4 affiliations
- 1Graduate School, Tianjin Medical University, Tianjin, People's Republic of China.
- 2Thoracic Surgery Clinical College, Tianjin Medical University, Tianjin, People's Republic of China.
- 3Graduate School, Tianjin University, Tianjin, People's Republic of China.
- 4Department of Thoracic Surgery, Tianjin Chest Hospital, Tianjin, People's Republic of China.
Abstract
Background
Integrative transcriptomic analyses can prioritize genes associated with chronic obstructive pulmonary disease (COPD), but expression associations require experimental assessment.Methods
Single-cell GSE173896 and bulk GSE57148 data were analyzed using clustering, co-expression networks, CellChat, differential expression, immune deconvolution, pseudotime, and virtual knockout analysis. A five-gene logistic nomogram was developed in GSE57148. Clinical RT-qPCR included 30 participants with COPD and 30 without COPD. Two independent IL6-targeting siRNAs were examined in HBEC3-KT and BEAS-2B cells using epithelial-macrophage co-culture, cytokine measurements, and wound-healing assays.Results
NHSL2, CDKL5, CRIP1, TNNI2, and IL6 were prioritized as candidate genes. Clinical RT-qPCR supported higher CDKL5, IL6, and NHSL2 expression and lower CRIP1 and TNNI2 expression in COPD. IL6 knockdown reduced epithelial IL6 expression and attenuated several macrophage-associated transcriptional responses in co-culture after epithelial cigarette smoke extract exposure. Secretory responses varied by cell line and siRNA; co-culture IL-10 reductions were significant in the HBEC3-KT system but not in the BEAS-2B system. IL6 knockdown also reduced epithelial wound closure. The nomogram was evaluated within its development cohort and lacked independent external validation.Conclusion
The study identifies five COPD-associated candidate genes and provides experimental evidence linking epithelial IL6 perturbation to selected co-culture responses and wound closure. These findings do not establish a COPD-specific mechanism or therapeutic benefit. The nomogram remains exploratory and requires independent validation.
Related
- Identification of transcriptomic signatures associated with an ac4C related gene set and candidate expression based clusters in osteoarthritis through integrative bioinformatics
- Identification of microglia-associated hub genes and a CX3CR1/P2RY12 two-gene diagnostic model for cross-subtype epilepsy-associated cortical malformations: integrated transcriptomic analysis with external validation
- Dynamic perioperative NPAR change for early identification of infectious complications after percutaneous nephrolithotomy: development and internal validation of a simple diagnostic model.
- An Oxidative Stress-Associated Seven-Gene Prognostic Signature in Lung Adenocarcinoma: Integrative Transcriptomic Analysis Across Public Cohorts
- Integrative Multi-Omics and Machine Learning Unveil Plakophilin 1 as a Robust Diagnostic Biomarker for Thymoma
BibTeX
@article{wang2026identification,
title = {{Identification of Five Candidate Genes and Development of an Exploratory Diagnostic Nomogram for COPD Using Integrative Single-Cell and Bulk Transcriptomic Analyses.}},
author = {Jianyu Wang and Han Zhang and Qiuqiao Mu and Xin Li and Daqiang Sun},
journal = {International journal of chronic obstructive pulmonary disease},
year = {2026},
month = oct,
doi = {10.2147/copd.s629378},
url = {https://europepmc.org/article/MED/42974151},
note = {CC BY-NC},
}
RIS
TY - JOUR
TI - Identification of Five Candidate Genes and Development of an Exploratory Diagnostic Nomogram for COPD Using Integrative Single-Cell and Bulk Transcriptomic Analyses.
AU - Jianyu Wang
AU - Han Zhang
AU - Qiuqiao Mu
AU - Xin Li
AU - Daqiang Sun
PY - 2026
DA - 2026/10/29
JO - International journal of chronic obstructive pulmonary disease
DO - 10.2147/copd.s629378
UR - https://europepmc.org/article/MED/42974151
AB - Background Integrative transcriptomic analyses can prioritize genes associated with chronic obstructive pulmonary disease (COPD), but expression associations require experimental assessment.Methods Single-cell GSE173896 and bulk GSE57148 data were analyzed using clustering, co-expression networks, CellChat, differential expression, immune deconvolution, pseudotime, and virtual knockout analysis. A five-gene logistic nomogram was developed in GSE57148. Clinical RT-qPCR included 30 participants with COPD and 30 without COPD. Two independent IL6-targeting siRNAs were examined in HBEC3-KT and BEAS-2B cells using epithelial-macrophage co-culture, cytokine measurements, and wound-healing assays.Results NHSL2, CDKL5, CRIP1, TNNI2, and IL6 were prioritized as candidate genes. Clinical RT-qPCR supported higher CDKL5, IL6, and NHSL2 expression and lower CRIP1 and TNNI2 expression in COPD. IL6 knockdown reduced epithelial IL6 expression and attenuated several macrophage-associated transcriptional responses in co-culture after epithelial cigarette smoke extract exposure. Secretory responses varied by cell line and siRNA; co-culture IL-10 reductions were significant in the HBEC3-KT system but not in the BEAS-2B system. IL6 knockdown also reduced epithelial wound closure. The nomogram was evaluated within its development cohort and lacked independent external validation.Conclusion The study identifies five COPD-associated candidate genes and provides experimental evidence linking epithelial IL6 perturbation to selected co-culture responses and wound closure. These findings do not establish a COPD-specific mechanism or therapeutic benefit. The nomogram remains exploratory and requires independent validation.
SN - 1176-9106
SN - 1178-2005
ER -