ECM2 and GLT8D2 in human pulmonary artery hypertension: fruits from weighted gene co-expression network analysis

Journal of Thoracic Disease

article

Zeyang Bai¹  Lianyan Xu³  Yong Dai¹  Qingchen Yuan¹  Zihua Zhou¹ 

[1] Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Key Lab of Molecular Biological Targeted Therapies of the Ministry of Education, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology;Department of Radiology, Peking Union Medical College Hospital, PUMC & CAMS

关键词: Pulmonary artery hypertension (PAH);    weighted gene coexpression network analysis (WGCNA);    hub gene;    ECM2;    GLT8D2;   

DOI  :  10.21037/jtd-20-3069

学科分类：呼吸医学

来源: Pioneer Bioscience Publishing Company

【 摘 要 】

Background: Pulmonary artery hypertension (PAH) is an incurable disease with a high mortality rate. Current medications ameliorate symptoms but cannot target adverse vascular remodeling. New therapeutic strategies for PAH need to be established. Methods: Using the weighted gene coexpression network analysis (WGCNA) algorithm, we constructed a coexpression network of dataset GSE117261 from the Gene Expression Omnibus (GEO) database. Key modules were identified by the relationship between module eigengenes and clinical traits. Hub genes were screened out based on gene significance (GS), module membership (MM), and mean pulmonary artery pressure (mPAP). External validations were conducted in GSE48149 and GSE113439. Functional enrichment and immune cell infiltration were analyzed using Metascape and CIBERSORTx. Results: The WGCNA analysis revealed 13 coexpression modules. The pink module had the highest correlation with PAH in terms of module eigengene (r=0.79; P=2e−18) and module significance (MS =0.43). Functional enrichment indicated genes in the pink module contributed to the immune system process and extracellular matrix (ECM). In the pink module, ECM2 (GS =0.65, MM =0.86, ρ=0.407, P=0.0019) and GLT8D2 (GS =0.63, MM =0.85, ρ=0.443, P=0.006) were identified as hub genes. For immune cells infiltration in PAH lung tissue, hub genes were positively correlated with M2 macrophages and resting mast cells, and were negatively correlated with monocytes, neutrophils, and CD4-naïve T cells. Conclusions: Our research identified 2 hub genes ECM2 and GLT8D2 related to PAH. The functions of these hub genes were involved in the immune process and ECM, indicating that they might serve as candidate therapeutic targets for PAH.

【 授权许可】

Unknown