Xie Zhefan, Xia Tingting, Wu Dongxue, Che Li, Zhang Wei, Cai Xingdong, Liu Shengming
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Jinan University, Guangzhou, China.
Ann Transl Med. 2022 Jun;10(12):665. doi: 10.21037/atm-22-2523.
Chronic obstructive pulmonary disease (COPD) is prevalent mainly in older adults, especially those who are smokers. It appears to be regulated by multiple genes, but there is some degree of familial clustering. The evidence to date suggests that COPD-associated biomarkers are largely inadequate for disease diagnosis, so we conducted a comprehensive search for more specific genetic markers.
We used 3 datasets from the Gene Expression Omnibus (GEO) database. By investigating the biological information [i.e., Gene Ontology, Kyoto Encyclopedia of Genes and Genomes and weighted gene co-expression network analysis (WGCNA)], we filtered out 8 differentially expressed genes (DEGs) and validated the transcript levels of those hub genes in 16HBE cell lines, THP-1 cell lines and lung tissue of COPD patients.
The 8 hub genes comprised amyloid precursor protein (), fibronectin 1, insulin-like growth factor 1 (), β-actin, capping actin protein of muscle Z-line subunit alpha 2, secreted phosphoprotein 1 (), catalase (), and colony stimulating factor 2 () were selected from among the DEGs. Cigarette smoke extract-stimulated 16HBE cells were found to highly express , and . In addition, levels were increased and and levels were decreased in CSE-stimulated THP-1 cells. and showed increased expression levels in lung tissue of COPD patients, but the opposite held for and .
We identified 8 hub genes of COPD based on GO, KEGG and WGCNA, which have provided insights into the pathophysiological mechanisms of COPD.
慢性阻塞性肺疾病(COPD)主要在老年人中流行,尤其是吸烟者。它似乎受多个基因调控,但存在一定程度的家族聚集性。迄今为止的证据表明,COPD相关生物标志物在很大程度上不足以用于疾病诊断,因此我们进行了全面搜索以寻找更特异的遗传标志物。
我们使用了来自基因表达综合数据库(GEO)的3个数据集。通过研究生物学信息[即基因本体论、京都基因与基因组百科全书以及加权基因共表达网络分析(WGCNA)],我们筛选出8个差异表达基因(DEGs),并在16HBE细胞系、THP-1细胞系和COPD患者的肺组织中验证了这些核心基因的转录水平。
从DEGs中选出了8个核心基因,包括淀粉样前体蛋白()、纤连蛋白1、胰岛素样生长因子1()、β-肌动蛋白、肌动蛋白帽蛋白Z线亚基α2、分泌性磷蛋白1()、过氧化氢酶()和集落刺激因子2()。发现香烟烟雾提取物刺激的16HBE细胞高表达、和。此外,在香烟烟雾提取物刺激的THP-1细胞中水平升高,而和水平降低。在COPD患者的肺组织中,和表达水平升高,但和则相反。
我们基于GO、KEGG和WGCNA鉴定出COPD的8个核心基因,这为深入了解COPD的病理生理机制提供了线索。