Abstract：
Most current research has focused on chronic obstructive pulmonary disease (COPD) and lung adenocarcinoma (LUAD) alone; however, it is important to understand the complex mechanism of COPD progression to LUAD. This study is the first to explore the unique and jointly molecular mechanisms in the pathogenesis of COPD and LUAD across several datasets based on a variety of analysis methods. We used weighted correlation network analysis to search hub genes in two datasets from public databases: GSE10072 and GSE76925. We explored the unique and jointly molecular mechanistic signatures of the two diseases in pathogenesis through enrichment analysis, immune infiltration analysis, and therapeutic targets analysis. Finally, the results were confirmed using real-time quantitative reverse transcription PCR. Fifteen hub genes were identified: GPI, EZH2, EFNA4, CFB, ENO1, SH3PXD2B, SELL, CORIN, MAD2L1, CENPF, TOP2A, ASPM, IGFBP2, CDKN2A, and ELF3. For the first time, SELL, CORIN, GPI, and EFNA4 were found to play a role in the etiology of COPD and LUAD. The LUAD genes identified were primarily involved in the cell cycle and DNA replication processes; COPD genes we found were related to ubiquitin-mediated proteolysis, ribosome, and T/B-cell receptor signaling pathways. The tumor microenvironment of LUAD pathogenesis was influenced by CD4 + T cells, type 1 regulatory T cells, and T helper 1 cells. T follicular helper cells, natural killer T cells, and B cells all impact the immunological inflammation in COPD. The results of drug targets analysis suggest that cisplatin and tretinoin, as well as bortezomib and metformin may be potential targeted therapy for patients with COPD combined LUAD. These signatures may be provided a new direction for developing early interventions and treatments to improve the prognosis of COPD and LUAD.
摘要：
目前大多数研究都集中在慢性阻塞性肺疾病（COPD）和肺腺癌（LUAD）上；然而，了解COPD进展为LUAD的复杂机制非常重要。本研究首次基于多种分析方法，在多个数据集上探索COPD和LUAD发病机制的独特和共同的分子机制。我们使用加权相关网络分析从公共数据库的两个数据集中搜索hub基因：GSE10072和GSE76925。我们通过富集分析探索了两种疾病在发病机制中的独特和共同的分子机制特征，免疫浸润分析，和治疗目标分析。最后,使用实时定量逆转录PCR证实了结果。确定了15个hub基因：GPI，EZH2,EFNA4,CFB,ENO1,SH3PXD2B,SELL,科林,MAD2L1,CENPF,TOP2A,ASPM,IGFBP2,CDKN2A,ELF3第一次,SELL,科林,GPI,和EFNA4被发现在COPD和LUAD的病因中起作用。鉴定的LUAD基因主要参与细胞周期和DNA复制过程；我们发现的COPD基因与泛素介导的蛋白水解有关，核糖体,和T/B细胞受体信号通路。LUAD发病机制的肿瘤微环境受CD4+T细胞、1型调节性T细胞,和T辅助细胞1。滤泡辅助性T细胞,自然杀伤T细胞,和B细胞均影响COPD的免疫炎症。药物靶标分析结果表明，顺铂和维甲酸，以及硼替佐米和二甲双胍可能是COPD合并LUAD患者的潜在靶向治疗。这些特征可能为开发早期干预和治疗以改善COPD和LUAD的预后提供新的方向。
