Department of Internal Medicine and Environmental Health Center, Kangwon National University Hospital, School of Medicine, Kangwon National University, Chuncheon 200-722, Republic of Korea.
Seoul National University Biomedical Informatics and Systems Biomedical Informatics Research Center, Division of Biomedical Informatics, Seoul National University College of Medicine, Seoul 110-799, Republic of Korea.
Int J Genomics. 2015;2015:206937. doi: 10.1155/2015/206937. Epub 2015 Mar 5.
Background and Objectives. Chronic obstructive pulmonary disease (COPD) is a complex disease characterized by airflow limitation. Although airway inflammation and oxidative stress are known to be important in the pathogenesis of COPD, the mechanism underlying airflow obstruction is not fully understood. Gene expression profiling of lung tissue was performed to define the molecular pathways that are dysregulated in COPD. Methods. RNA was isolated from lung tissues obtained from 98 subjects with COPD and 91 control subjects with normal spirometry. The RNA samples were processed with RNA-seq using the HiSeq 2000 system. Genes expressed differentially between the two groups were identified using Student's t-test. Results. After filtering for genes with zero counts and noncoding genes, 16,676 genes were evaluated. A total of 2312 genes were differentially expressed between the lung tissues of COPD and control subjects (false discovery rate corrected q < 0.01). The expression of genes related to oxidative phosphorylation and protein catabolism was reduced and genes related to chromatin modification were dysregulated in lung tissues of COPD subjects. Conclusions. Oxidative phosphorylation, protein degradation, and chromatin modification were the most dysregulated pathways in the lung tissues of COPD subjects. These findings may have clinical and mechanistic implications in COPD.
慢性阻塞性肺疾病（COPD）是一种以气流受限为特征的复杂疾病。尽管气道炎症和氧化应激已知在 COPD 的发病机制中起重要作用，但气流受限的机制仍不完全清楚。本研究通过对肺组织进行基因表达谱分析，以确定 COPD 中失调的分子途径。方法：从 98 例 COPD 患者和 91 例肺功能正常的对照者的肺组织中提取 RNA。使用 HiSeq 2000 系统对 RNA 样本进行 RNA-seq 处理。使用 Student's t 检验鉴定两组间差异表达的基因。结果：在剔除零计数基因和非编码基因后，共评估了 16676 个基因。COPD 患者与对照组肺组织中共有 2312 个基因存在差异表达（校正后的假发现率 q < 0.01）。COPD 患者肺组织中与氧化磷酸化和蛋白质分解代谢相关的基因表达下调，与染色质修饰相关的基因失调。结论：氧化磷酸化、蛋白质降解和染色质修饰是 COPD 患者肺组织中失调最明显的途径。这些发现可能对 COPD 的临床和机制具有重要意义。
