Denkçeken Tuba, Pala Elif
Department of Biophysics, Faculty of Medicine, SANKO University, Gaziantep, Turkey.
Gen Physiol Biophys. 2020 Jan;39(1):69-77. doi: 10.4149/gpb_2019042.
Lung cancer (LC) is the prominent cause of cancer-related death worldwide, and non-small cell lung cancer (NSCLC) represents approximately 85% of all diagnosed LC cases. It is stated that LC and chronic obstructive pulmonary disease (COPD) are directly linked at a molecular genetics level. Early diagnosis of LC is important for individuals affected by COPD. This study aims to construct a molecular network to discover molecules in NSCLC development from COPD. We downloaded the expression profiles of COPD patients from Gene Expression Omnibus database. The Database Annotation for Visualization and Integrated Discovery tool was utilized for enrichment analysis; STRING and Cytoscape were used for network construction. 15 hub genes were detected among 1517 differentially expressed genes (DEGs). Additionally, 20 differentially expressed miRNAswere identified from five datasets. We constructed miRNA-mRNA regulatory network between the groups of overlapping predicted target genes/DEGs and miRNAs that contained miRNA-mRNA pairs. UALCAN and OncomiR web-portals were used to validate hub genes and miRNAs in NSCLC. JUN, IL6, CD4 and hsa-miR-497-5p, hsa-miR-130b-5p were verified in both lung adenocarcinomas and lung squamous cell carcinomas. This study presents potential biomarkers and mechanisms underlying NSCLC development from COPD that would be targeted for early intervention.
肺癌（LC）是全球癌症相关死亡的主要原因，非小细胞肺癌（NSCLC）约占所有确诊LC病例的85%。据指出，LC与慢性阻塞性肺疾病（COPD）在分子遗传学水平上直接相关。LC的早期诊断对受COPD影响的个体很重要。本研究旨在构建一个分子网络，以发现COPD发展为NSCLC过程中的分子。我们从基因表达综合数据库下载了COPD患者的表达谱。利用数据库注释可视化与综合发现工具进行富集分析；使用STRING和Cytoscape构建网络。在1517个差异表达基因（DEG）中检测到15个枢纽基因。此外，从五个数据集中鉴定出20个差异表达的miRNA。我们在重叠预测靶基因/DEG和包含miRNA-mRNA对的miRNA组之间构建了miRNA-mRNA调控网络。使用UALCAN和OncomiR网站验证NSCLC中的枢纽基因和miRNA。JUN、IL6、CD4以及hsa-miR-497-5p、hsa-miR-130b-5p在肺腺癌和肺鳞状细胞癌中均得到验证。本研究提出了COPD发展为NSCLC的潜在生物标志物和潜在机制，这些将作为早期干预的靶点。
