Abstract
BACKGROUND: Immune cells and metabolites significantly impact organism health and disease processes. The interaction between non-small cell lung cancer (NSCLC) and metabolites and immune cells remains underexplored. METHODS: To investigate the causal relationships between immune cells, metabolites, and NSCLC, we used Mendelian randomization (MR). The research design comprehensively embraced the direct correlation and the role that metabolites play as an intermediate in the interaction between NSCLC and immune cells. RESULTS: MR analysis allowed us to finally identify one immune cell, there was a substantial causal connection between CD64 on CD14⁻CD16⁻ and NSCLC. Furthermore, we discovered four metabolites that showed strong causal links to NSCLC: 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (p-18:0/20:4) levels, phenyllactate (PLA) levels in elite athletes, the caffeine to paraxanthine ratio and 1-palmitoyl-2-arachidonoyl-GPC (16:0/20:4n6) levels. Finally, through a two-step MR mediation analysis, we found that CD64 on CD14⁻CD16⁻ mediated the occurrence of NSCLC via 1-palmitoleoyl-2-linolenoyl-GPC (16:1/18:3) levels and the caffeine to paraxanthine ratio, with mediation proportions of - 11.89% and 21.69%, respectively. CONCLUSION: Our findings show the complicated link between immune cells, metabolites, and NSCLC. The discovered connections and mediating effects provide important insights.