Division of Biomedical Convergence, College of Biomedical Science, Institute of Bioscience & Biotechnology, Kangwon National University, Chuncheon 24341, Korea.
Department of Internal Medicine, School of Medicine, Kangwon National University, Chuncheon 24341, Korea.
Mol Cells. 2019 Apr 30;42(4):333-344. doi: 10.14348/molcells.2019.2442.
Various genetic and environmental factors are known to be associated with chronic obstructive pulmonary disease (COPD). We identified COPD-related differentially expressed genes (DEGs) using 189 samples accompanying either adenocarcinoma (AC) or squamous cell carcinoma (SC), comprising 91 normal and 98 COPD samples. DEGs were obtained from the intersection of two DEG sets separately identified for AC and SC to exclude the influence of different cancer backgrounds co-occurring with COPD. We also measured patient samples named group 'I', which were unable to be determined as normal or COPD based on alterations in gene expression. The Gene Ontology (GO) analysis revealed significant alterations in the expression of genes categorized with the 'cell adhesion', 'inflammatory response', and 'mitochondrial functions', i.e., well-known functions related to COPD, in samples from patients with COPD. Multi-omics data were subsequently integrated to decipher the upstream regulatory changes linked to the gene expression alterations in COPD. COPD-associated expression quantitative trait loci (eQTLs) were located at the upstream regulatory regions of 96 DEGs. Additionally, 45 previously identified COPD-related miRNAs were predicted to target 66 of the DEGs. The eQTLs and miRNAs might affect the expression of 'respiratory electron transport chain' genes and 'cell proliferation' genes, respectively, while both eQTLs and miRNAs might affect the expression of 'apoptosis' genes. We think that our present study will contribute to our understanding of the molecular etiology of COPD accompanying lung cancer.
已知多种遗传和环境因素与慢性阻塞性肺疾病（COPD）有关。我们使用 189 个伴随腺癌（AC）或鳞状细胞癌（SC）的样本，包括 91 个正常样本和 98 个 COPD 样本，鉴定了 COPD 相关的差异表达基因（DEG）。DEG 是从分别为 AC 和 SC 确定的两个 DEG 集合的交集获得的，以排除与 COPD 同时发生的不同癌症背景的影响。我们还测量了命名为“ I”组的患者样本，这些样本无法根据基因表达的改变确定为正常或 COPD。基因本体论（GO）分析表明，COPD 患者样本中与“细胞黏附”、“炎症反应”和“线粒体功能”相关的基因表达发生了显著改变，即与 COPD 相关的已知功能。随后整合多组学数据以解析与 COPD 基因表达改变相关的上游调控变化。COPD 相关的表达数量性状基因座（eQTLs）位于 96 个 DEG 的上游调控区域。此外，预测了 45 个先前确定的 COPD 相关 miRNA 靶向 66 个 DEG。eQTLs 和 miRNAs 可能分别影响“呼吸电子传递链”基因和“细胞增殖”基因的表达，而 eQTLs 和 miRNAs 可能都影响“凋亡”基因的表达。我们认为我们的研究将有助于我们理解伴随肺癌的 COPD 的分子病因。
