Department of Respiratory Medicine, Liyuan Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 39 Yanhu Avenue, Wuchang District, Wuhan, 430000, Hubei, China.
Institute of Genomic Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang, China.
Sci Rep. 2022 Aug 2;12(1):13214. doi: 10.1038/s41598-022-17552-x.
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.
大多数当前的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。这项研究首次基于多种分析方法，利用来自公共数据库的两个数据集（GSE10072 和 GSE76925），通过加权相关网络分析，探索 COPD 和 LUAD 发病机制中的独特和共同分子机制。我们通过富集分析、免疫浸润分析和治疗靶点分析，探讨了两种疾病在发病机制中的独特和共同分子机制特征。最后，使用实时定量逆转录 PCR 对结果进行了验证。共鉴定出 15 个枢纽基因：GPI、EZH2、EFNA4、CFB、ENO1、SH3PXD2B、SELL、CORIN、MAD2L1、CENPF、TOP2A、ASPM、IGFBP2、CDKN2A 和 ELF3。首次发现 SELL、CORIN、GPI 和 EFNA4 参与 COPD 和 LUAD 的发病机制。鉴定出的 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、核糖体和 T/B 细胞受体信号通路有关。LUAD 发病机制中的肿瘤微环境受 CD4+T 细胞、1 型调节性 T 细胞和辅助性 T 细胞 1 的影响。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。药物靶点分析的结果表明，顺铂和维甲酸以及硼替佐米和二甲双胍可能是 COPD 合并 LUAD 患者潜在的靶向治疗药物。这些特征可能为开发早期干预和治疗方法提供新的方向，以改善 COPD 和 LUAD 的预后。
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