Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration

作者：Dengfeng Zhang, Haitao Liu, Fangchao Zhao, Pengfei Guo, Jing Li, Tianxing Lu, Zhirong Li, Shujun Li · 发表于：BMC Cancer · 年份：2024 · DOI：10.1186/s12885-024-12076-1 · 被引用次数：11 · 研究领域：Chronic Obstructive Pulmonary Disease (COPD) Research、Genetic Associations and Epidemiology、Ferroptosis and cancer prognosis

BACKGROUND: Evidence from observational studies suggests an association between chronic obstructive pulmonary disease (COPD) and lung cancer. The potential interactions between the immune system and the lungs may play a causative role in COPD and lung cancer and offer therapeutic prospects. However, the causal association and the immune-mediated mechanisms between COPD and lung cancer remain to be determined. METHODS: We employed a two-sample Mendelian randomization (MR) approach to investigate the causal association between COPD and lung cancer. Additionally, we examined whether immune cell signals were causally related to lung cancer, as well as whether COPD was causally associated with immune cell signals. Furthermore, through two-step Mendelian randomization, we investigated the mediating effects of immune cell signals in the causal association between COPD and lung cancer. Leveraging publicly available genetic data, our analysis included 468,475 individuals of European ancestry with COPD, 492,803 individuals of European ancestry with lung cancer, and 731 immune cell signatures of European ancestry. Additionally, we conducted single-cell transcriptome sequencing analysis on COPD, lung cancer, and control samples to validate our findings. FINDINGS: We found a causal association between COPD and lung cancer (odds ratio [OR] = 1.63, 95% confidence interval [CI] = 1.31-2.02, P-value < 0.001). We also observed a causal association between COPD and regulatory T cells (odds rati...