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Identification of hub genes and key pathways in the emphysema phenotype of COPD.

Abstract
Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition associated with high morbidity and mortality. This study aimed to use weighted gene co-expression network analysis (WGCNA) to explore the molecular pathogenesis of the emphysema phenotype of COPD. After obtaining lung mRNA expression profiles from ten patients with the emphysema phenotype of COPD and eight controls, emphysema-associated gene modules were identified with WGCNA. Among 13 distinct modules, the green-yellow and brown modules showed the strongest correlations with emphysema severity and lung function and were thus selected as hub modules. On gene ontology analysis, these two modules were mainly enriched in immune response, B cell receptor (BCR) signaling pathway, extracellular matrix (ECM) organization, and collagen fibril organization. Pathway analysis primarily showed enrichment in BCR signaling pathways, ECM receptor interaction, and NF-κB and TGF-β signaling pathways for the two hub modules. Several genes, including FCRLA, MS4A1, CD19, FKBP10, C1S and HTRA1, among others, were identified as hub genes. Our results shed light on the potential genetic mechanisms underlying the pathogenesis of the emphysema phenotype of COPD. However, further research will be needed to confirm the involvement of the identified genes and to determine their therapeutic relevance.
AuthorsQiunan Zuo, Youyu Wang, Deqing Yang, Shujin Guo, Xiaohui Li, Jiajia Dong, Chun Wan, Yongchun Shen, Fuqiang Wen
JournalAging (Aging (Albany NY)) Vol. 13 Issue 4 Pg. 5120-5135 (02 01 2021) ISSN: 1945-4589 [Electronic] United States
PMID33535173 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Antigens, CD19
  • FCRLA protein, human
  • NF-kappa B
  • RNA, Messenger
  • Receptors, Antigen, B-Cell
  • Receptors, Fc
  • Transforming Growth Factor beta
  • High-Temperature Requirement A Serine Peptidase 1
  • HTRA1 protein, human
  • Complement C1s
  • Tacrolimus Binding Proteins
  • FKBP10 protein, human
Topics
  • Aged
  • Antigens, CD19 (genetics)
  • Case-Control Studies
  • Complement C1s (genetics)
  • Extracellular Matrix (genetics)
  • Female
  • Gene Regulatory Networks
  • High-Temperature Requirement A Serine Peptidase 1 (genetics)
  • Humans
  • Male
  • Middle Aged
  • NF-kappa B (genetics)
  • Pulmonary Disease, Chronic Obstructive (genetics, metabolism)
  • Pulmonary Emphysema (genetics, metabolism)
  • RNA, Messenger
  • Receptors, Antigen, B-Cell (genetics)
  • Receptors, Fc (genetics)
  • Tacrolimus Binding Proteins (genetics)
  • Transcriptome
  • Transforming Growth Factor beta (genetics)

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