Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration
Abstract 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....
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-04-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-024-12076-1 |
| _version_ | 1797209280870350848 |
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| author | Dengfeng Zhang Haitao Liu Fangchao Zhao Pengfei Guo Jing Li Tianxing Lu Zhirong Li Shujun Li |
| author_facet | Dengfeng Zhang Haitao Liu Fangchao Zhao Pengfei Guo Jing Li Tianxing Lu Zhirong Li Shujun Li |
| author_sort | Dengfeng Zhang |
| collection | DOAJ |
| description | Abstract 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 ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01–1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002–1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. Interpretation As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role. |
| first_indexed | 2024-04-24T09:52:12Z |
| format | Article |
| id | doaj.art-6531661ff4e14cc5842c38e3ab0d209b |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-04-24T09:52:12Z |
| publishDate | 2024-04-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-6531661ff4e14cc5842c38e3ab0d209b2024-04-14T11:18:55ZengBMCBMC Cancer1471-24072024-04-012411910.1186/s12885-024-12076-1Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integrationDengfeng Zhang0Haitao Liu1Fangchao Zhao2Pengfei Guo3Jing Li4Tianxing Lu5Zhirong Li6Shujun Li7Provincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityCollege of Life Science, Inner Mongolia UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityProvincial Center for Clinical Laboratories，Department of Thoracic Surgery, The Second Hospital of Hebei Medical UniversityAbstract 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 ratio [OR] = 1.19, 95% confidence interval [CI] = 1.01–1.40, P-value < 0.05), as well as a causal association between regulatory T cells and lung cancer (odds ratio [OR] = 1.02, 95% confidence interval [CI] = 1.002–1.045, P-value < 0.05). Furthermore, our two-step Mendelian randomization analysis demonstrated that COPD is associated with lung cancer through the mediation of regulatory T cells. These findings were further validated through single-cell sequencing analysis, confirming the mediating role of regulatory T cells in the association between COPD and lung cancer. Interpretation As far as we are aware, we are the first to combine single-celled immune cell data with two-sample Mendelian randomization. Our analysis indicates a causal association between COPD and lung cancer, with regulatory T cells playing an intermediary role.https://doi.org/10.1186/s12885-024-12076-1scRNA-seqMendelian randomizationLung cancerRegulatory T cellsChronic obstructive Pulmonary disease |
| spellingShingle | Dengfeng Zhang Haitao Liu Fangchao Zhao Pengfei Guo Jing Li Tianxing Lu Zhirong Li Shujun Li Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration BMC Cancer scRNA-seq Mendelian randomization Lung cancer Regulatory T cells Chronic obstructive Pulmonary disease |
| title | Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration |
| title_full | Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration |
| title_fullStr | Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration |
| title_full_unstemmed | Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration |
| title_short | Exploring the relationship between Treg-mediated risk in COPD and lung cancer through Mendelian randomization analysis and scRNA-seq data integration |
| title_sort | exploring the relationship between treg mediated risk in copd and lung cancer through mendelian randomization analysis and scrna seq data integration |
| topic | scRNA-seq Mendelian randomization Lung cancer Regulatory T cells Chronic obstructive Pulmonary disease |
| url | https://doi.org/10.1186/s12885-024-12076-1 |
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