Causal association of plasma lipidome with lung carcinoma and mediating role of inflammatory proteins: evidence from Mendelian randomization analysis

The evidence from clinical studies suggests that lung carcinoma (LC) patients exhibit dysregulation in lipid metabolism. However, the causal relationship between plasma lipidome and LC, and whether inflammatory proteins mediate, remains to be determined. Genetic data for 179 plasma lipids and 91 inflammatory proteins were obtained from the latest published genome-wide association studies. Genetic data on LC and subtypes were from the largest available meta-analysis. The causal relationship between plasma lipidome and LC was determined by the two-sample Mendelian randomization (MR) method. Mediation MR analysis was employed to ascertain whether inflammatory proteins mediate the impact of plasma lipidome on LC. We identified 39 causal relationships between genetically predicted plasma lipidome and LC and subtypes. These relationships involve the influence of phosphatidylcholines, phosphatidylethanolamines, diacylglycerols, triacylglycerols, sphingomyelins, and Sterol esters. Additionally, the mediating role of 5 inflammatory proteins in the causal relationship between plasma lipidome and LC and subtypes was determined. Our results highlight the complex network of plasma lipidome and inflammatory proteins regulating LC. Integrating plasma lipidome and inflammatory proteins into clinical practice may open new avenues for the prevention and treatment of LC.