Content area

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.

Details

Title
Relationships among immune cells, metabolites, and non-small cell lung cancer: a mediation Mendelian randomization study
Pages
501
Publication year
2025
Publication date
Dec 2025
Publisher
Springer Nature B.V.
e-ISSN
27306011
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3189542958
Copyright
Copyright Springer Nature B.V. Dec 2025