ArticleMedicine2025
Liposomes, immune cells, and lung cancer subtypes: A bidirectional Mendelian randomization study.
Article in Medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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7 authors.
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Abstract
Alterations in lipid metabolism and immune cell functions have gained attention for their impact on the tumor microenvironment. However, the causal relationships between lipids and immune cells in lung cancer subtypes remain unclear. This study utilized plasma lipidomics summary data from genome-wide association studies, immune phenotypic data from the European Bioinformatics Institute, and comprehensive statistics of different lung cancer subtypes from the International Lung Cancer Consortium and the Transdisciplinary Research in Cancer of the Lung (TRICL). Two-sample Mendelian randomization and Bayesian weighted Mendelian randomization were applied to explore causal links between lipids and lung cancer subtypes. Sensitivity tests ensured robustness, and mediation analysis assessed immune cell roles. We identified causal relationships between 12 lipids, 59 immune cells, and lung cancer subtypes. Further mediation analysis showed that phosphatidylcholine (O-16:1_18:0) significantly reduced the risk of lung cancer through the CD14- CD16+ monocyte mediator (International Lung Cancer Consortium [ILCCO]: 11.11%, TRICL: 6.03%); the risk reduction through the CD16+ monocyte mediator was (ILCCO: 6.43%, TRICL: 6.67%). In squamous cell lung cancer, this lipid mediated a risk reduction via CD14- CD16+ monocyte (ILCCO: 8.30%, TRICL: 5.89%), via CD123 on plasmacytoid dendritic cell (ILCCO: 5.93%, TRICL: 4.48%), and via CD123 on CD62L+ plasmacytoid dendritic cell (ILCCO: 5.86%, TRICL: 4.43%). In contrast, phosphatidylcholine (O-16:0_20:3) levels increased the risk of small cell lung cancer via CD4 on CD39+ activated regulatory T cell (ILCCO: 10.33%, TRICL: 9.98%). Phosphatidylcholine regulates lung cancer risk through immune cells, highlighting its potential as a precise nano-targeted immunotherapy for lung cancer subtypes.
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