Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study
Abstract Background This study utilized Mendelian randomization (MR) to investigate the causal relationship between circulating plasma proteins and lung adenocarcinoma. Methods We obtained 734 circulating plasma protein data from genome-wide association studies (GWAS) as exposure factors and extract...
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BMC
2025-06-01
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| Series: | BMC Pulmonary Medicine |
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| Online Access: | https://doi.org/10.1186/s12890-025-03751-5 |
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| author | Weiyuan Zhang Nan Chen Changxi Li Xitian Su Zhuo Fu Youshuang Zhong Huojin Deng |
| author_facet | Weiyuan Zhang Nan Chen Changxi Li Xitian Su Zhuo Fu Youshuang Zhong Huojin Deng |
| author_sort | Weiyuan Zhang |
| collection | DOAJ |
| description | Abstract Background This study utilized Mendelian randomization (MR) to investigate the causal relationship between circulating plasma proteins and lung adenocarcinoma. Methods We obtained 734 circulating plasma protein data from genome-wide association studies (GWAS) as exposure factors and extracted single nucleotide polymorphisms (SNPs) as instrumental variables. And we obtained lung adenocarcinoma data (including 11,245 cases and 54,619 controls) from the IEU Open GWAS database as the outcome factor. The main analytical methods used are inverse-variance weighted (IVW) or Wald ratio to assess the causal relationship between circulating plasma protein levels and lung adenocarcinoma. Sensitivity analysis (leave one out method, heterogeneity and pleiotropy tests), external validation analysis, and meta-analysis after MR were used to evaluate the reliability of MR results. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the final screened plasma proteins. Results Through the preliminary and external validation stages, ICAM5 (OR = 0.92, 95%CI: 0.89–0.95, P = 2.31 × 10–6), PCYOX1 (OR = 0.89, 95%CI: 0.85–0.93, P = 5.31 × 10–8), and TYMP (OR = 0.76, 95%CI: 0.66–0.87, P = 5.79 × 10–5) are negatively correlated with lung adenocarcinoma. Sensitivity analyses, external validation, and post-MR meta-analysis indicated that the MR results were robust. GO and KEGG pathway enrichment analyses demonstrated that these plasma proteins were primarily enriched in pathways such as "pyrimidine deoxyribonucleoside monophosphate metabolic process", "deoxyribonucleoside monophosphate catabolic process", "mitochondrial genome maintenance", and "Pyrimidine metabolism". Conclusions ICAM5, PCYOX1 and TYMP are associated with a decreased risk of lung adenocarcinoma. Plasma proteins may become new biological markers for lung adenocarcinoma, providing new insights into the prevention and treatment of this disease. |
| format | Article |
| id | doaj-art-4596bfaf47024707bddadf4988c32a91 |
| institution | OA Journals |
| issn | 1471-2466 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | BMC Pulmonary Medicine |
| spelling | doaj-art-4596bfaf47024707bddadf4988c32a912025-08-20T02:05:46ZengBMCBMC Pulmonary Medicine1471-24662025-06-012511910.1186/s12890-025-03751-5Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization studyWeiyuan Zhang0Nan Chen1Changxi Li2Xitian Su3Zhuo Fu4Youshuang Zhong5Huojin Deng6Department of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityDepartment of Pulmonary and Critical Care Medicine, Zhujiang Hospital, Southern Medical UniversityAbstract Background This study utilized Mendelian randomization (MR) to investigate the causal relationship between circulating plasma proteins and lung adenocarcinoma. Methods We obtained 734 circulating plasma protein data from genome-wide association studies (GWAS) as exposure factors and extracted single nucleotide polymorphisms (SNPs) as instrumental variables. And we obtained lung adenocarcinoma data (including 11,245 cases and 54,619 controls) from the IEU Open GWAS database as the outcome factor. The main analytical methods used are inverse-variance weighted (IVW) or Wald ratio to assess the causal relationship between circulating plasma protein levels and lung adenocarcinoma. Sensitivity analysis (leave one out method, heterogeneity and pleiotropy tests), external validation analysis, and meta-analysis after MR were used to evaluate the reliability of MR results. Finally, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on the final screened plasma proteins. Results Through the preliminary and external validation stages, ICAM5 (OR = 0.92, 95%CI: 0.89–0.95, P = 2.31 × 10–6), PCYOX1 (OR = 0.89, 95%CI: 0.85–0.93, P = 5.31 × 10–8), and TYMP (OR = 0.76, 95%CI: 0.66–0.87, P = 5.79 × 10–5) are negatively correlated with lung adenocarcinoma. Sensitivity analyses, external validation, and post-MR meta-analysis indicated that the MR results were robust. GO and KEGG pathway enrichment analyses demonstrated that these plasma proteins were primarily enriched in pathways such as "pyrimidine deoxyribonucleoside monophosphate metabolic process", "deoxyribonucleoside monophosphate catabolic process", "mitochondrial genome maintenance", and "Pyrimidine metabolism". Conclusions ICAM5, PCYOX1 and TYMP are associated with a decreased risk of lung adenocarcinoma. Plasma proteins may become new biological markers for lung adenocarcinoma, providing new insights into the prevention and treatment of this disease.https://doi.org/10.1186/s12890-025-03751-5Mendelian randomizationPlasma proteinsLung adenocarcinoma |
| spellingShingle | Weiyuan Zhang Nan Chen Changxi Li Xitian Su Zhuo Fu Youshuang Zhong Huojin Deng Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study BMC Pulmonary Medicine Mendelian randomization Plasma proteins Lung adenocarcinoma |
| title | Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study |
| title_full | Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study |
| title_fullStr | Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study |
| title_full_unstemmed | Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study |
| title_short | Causal association between plasma proteins and lung adenocarcinoma: a two-sample mendelian randomization study |
| title_sort | causal association between plasma proteins and lung adenocarcinoma a two sample mendelian randomization study |
| topic | Mendelian randomization Plasma proteins Lung adenocarcinoma |
| url | https://doi.org/10.1186/s12890-025-03751-5 |
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