WCLC 2025 - Posters & ePosters-P3.01.04 Bootstrap-Based Mediation Mendelian Randomization Unveils Gut Microbiota-Driven Metabolic-Immune Networks in Lung Cancer

P3.01.04 Bootstrap-Based Mediation Mendelian Randomization Unveils Gut Microbiota-Driven Metabolic-Immune Networks in Lung Cancer

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Pdf Summary

This study by Peng et al. introduces a novel bootstrap-based Mendelian Randomization (MR) mediation method to robustly validate mediation effects, addressing limitations in traditional MR analyses. Utilizing data from 15 genome-wide association studies (GWAS), the authors focused on the gut microbiota–metabolome–immune–lung cancer axis, a key regulatory network in lung cancer pathogenesis.<br /><br />The bootstrap approach demonstrated excellent agreement with conventional MR mediation results, with an intraclass correlation coefficient of 1.000 and Spearman correlation of 0.999 (p=0.001), indicating high consistency and reliability. This validation method also helped exclude inconsistent findings from previous analyses.<br /><br />Key findings identified Herbinix abundance as a gut microbiota factor that elevates plasma total lipids in lipoprotein particles and increases CCR2 expression on CD62L myeloid dendritic cells. These changes were linked to a reduced risk of lung cancer, with an odds ratio of 1.004 (95% CI: 1.000–1.007). The study thus reveals multiple mediation pathways connecting gut microbiota, plasma metabolites, immune cells, and lung cancer development.<br /><br />The results were consistent across various lung cancer subtypes, including non-small cell lung cancer (NSCLC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC), large cell neuroendocrine carcinoma (LUNE), and small cell lung cancer (SCLC).<br /><br />In conclusion, this research presents a statistically rigorous bootstrap-based MR mediation framework that enhances the reliability of causal inference in complex biological pathways. It uncovers numerous gut microbiota-driven metabolic and immune regulatory networks influencing lung cancer risk, offering potential targets for future diagnostic and therapeutic strategies.

Asset Subtitle

Ying-Long Peng

Meta Tag

Speaker Ying-Long Peng

Topic Risk Factors, Risk Reduction & Tobacco Control

Keywords

bootstrap-based Mendelian Randomization

mediation analysis

gut microbiota

lung cancer

genome-wide association studies

Herbinix abundance

plasma metabolites

immune regulation

lung cancer subtypes

causal inference