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To investigate the causal relationship between immune cell mediated liposomes and non-small cell lung cancer (NSCLC) using two-sample Mendelian randomization and two-step analysis.
Summary data of GWAS for plasma liposomes were obtained from the GWAS Catalog as exposure data. Summary data of GWAS for 731 types of immune cells were selected as potential mediators, and NSCLC data from the ninth release of the FinnGen database were used as outcome data. Inverse-variance weighted (IVW) was used for two-step. Two-sample Mendelian randomization analysis was used to investigate the causal relationship between liposomes and NSCLC and the mediating role of immune cells in the lipid-NSCLC association. Weighted median and MR-Egger methods were used as supplements, along with pleiotropy and heterogeneity tests to ensure result stability.
The IVW method identified 36 liposomes associated with NSCLC, with no evidence of reverse causation. A total of 47 immune cell types were strongly associated with NSCLC. Notably, triglyceride (TG) (58:8) had a causal effect on NSCLC (OR=1.183, 95%CI: 1.061-1.319). The mediation effect mediated by Effector Memory CD8+ T cell %CD8+ T cell was 0.003 (95%CI: -0.007-0.013), accounting for 1.94% of the total effect, while the mediation effect mediated by CD8+ and CD8dim T cell %leukocyte was 0.012 (95%CI: -0.004-0.028), accounting for 7.24% of the total effect.
This study suggests a causal relationship between liposomes and NSCLC, identifying TG as a risk factor for NSCLC progression. Effector Memory CD8+ T cell %CD8+ T cell and CD8+ CD8dim T cell %leukocyte play a mediating role in this process.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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