Research Paper Volume 14, Issue 20 pp 8568—8580

Identification and validation of genetic signature associated with aging in chronic obstructive pulmonary disease

Shanshan Chen1, *, , Yuan Zhan1, *, , Jinkun Chen2, , Jixing Wu1, , Yiya Gu1, , Qian Huang1, , Zhesong Deng1, , Xiaojie Wu3, , Yongman Lv4, , Jungang Xie1, &, ,

  • 1 Department of Respiratory and Critical Care Medicine, National Clinical Research Center of Respiratory Disease, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
  • 2 Department of Science, Western University, London, Ontario N6A 3K7, Canada
  • 3 Department of Respiratory and Critical Care Medicine, Wuhan No.1 Hospital, Wuhan Hospital of Traditional Chinese and Western Medicine, Wuhan 430022, China
  • 4 Health Management Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei, China
* Equal contribution

Received: March 16, 2022       Accepted: October 12, 2022       Published: October 28, 2022
How to Cite

Copyright: © 2022 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Aging plays an essential role in the development for chronic obstructive pulmonary disease (COPD). The aim of this study was to identify and validate the potential aging-related genes of COPD through bioinformatics analysis and experimental validation. Firstly, we compared the gene expression profiles of aged and young COPD patients using two datasets (GSE76925 and GSE47460) from Gene Expression Omnibus (GEO), and identified 244 aging-related different expressed genes (DEGs), with 132 up-regulated and 112 down-regulated. Then, by analyzing the data for cigarette smoke-induced COPD mouse model (GSE125521), a total of 783 DEGs were identified between aged and young COPD mice, with 402 genes increased and 381 genes decreased. Additionally, functional enrichment analysis revealed that these DEGs were actively involved in COPD-related biological processes and function pathways. Meanwhile, six genes were identified as the core aging-related genes in COPD after combining the human DEGs and mouse DEGs. Eventually, five out of six core genes were validated to be up-regulated in the lung tissues collected from aged COPD patients than young COPD patients, namely NKG7, CKLF, LRP4, GDPD3 and CXCL9. Thereinto, the expressions of NKG7 and CKLF were negatively associated with lung function. These results may expand the understanding for aging in COPD.


COPD: chronic obstructive pulmonary disease; GEO: gene expression omnibus; DEGs: differently expressed genes; GO: gene ontology; KEGG: Kyoto Encyclopedia of Genes and Genomes; BP: biological process; CC: cell component; MF: molecular function; NKG7: natural killer cell granule protein 7; CKLF: chemokine like factor; LRP4: LDL receptor related protein 4; MLF1: myeloid leukemia factor 1; GDPD3: glycerophosphodiester phosphodiesterase domain containing 3; CXCL9: C-X-C motif chemokine ligand 9; ECM: extracellular matrix; PAH: pulmonary arterial hypertension; CTEPAH: chronic thromboembolic pulmonary arterial hypertension; HIP1: huntingtin-interacting protein 1.