血浆SPARC介导的外周血嗜酸性粒细胞在胃癌中的作用:基于多变量孟德尔随机化研究和中介分析OACSTPCD

Objective East Asia exhibits one of the highest global incidence rates of gastric cancer.The intricate relationship between peripheral blood immune cell counts and the onset and progression of gastric cancer is often obscured by reverse causality and confounders.This study em-ploys Mendelian randomization analysis to mitigate associated biases,aiming to elucidate the causal connection between peripheral immune cell counts and gastric cancer.Methods Both univariate and multivariate Mendelian randomization methods were employed to explore the causal relationship between diverse immune cell subtypes in peripheral blood and the risk of gastric cancer using data from Genome-wide association studies(GWAS).Exposure factors included counts of white blood cells,granulocytes,neutrophils,eosinophils,basophils,lymphocytes,and monocytes.The pri-mary approach for univariate Mendelian randomization analysis involved the inverse variance-weigh-ted method.Afterwards,a two-step mediation analysis was conducted to investigate the potential role of plasma proteins in this process.Results Mendelian randomization analysis revealed a causal rela-tionship between lymphocytes(OR = 1.094,95%CI:1.009-1.185,P = 0.029)and eosino-phils(OR = 0.881,95%CI:0.813-0.955,P = 0.002)and the incidence of gastric canc-er.Sensitivity analysis corroborated the reliability of these results.Furthermore,the association be-tween decreased eosinophil counts and a reduced risk of gastric cancer persisted in multivariate Men-delian randomization analysis(OR =0.807,95%CI:0.671-0.970,P =0.023).Reverse cau-sality was not significant.The secreted protein acidic and rich in cysteine(SPARC)is an extracel-lular matrix protein that involves in various cell-matrix interactions and cellular signaling pathways,playing a significant role in tumor development.The mediation analysis of 1 124 plasma proteins sug-gested that plasma SPARC might mediate the protective effect of eosinophils against gastric cancer(Beta =-0.030,95%CI:-0.072-0.000,P =0.024).Conclusion Mendelian randomization analysis establishes eosinophil counts as an independent factor in diminishing the incidence of gastric cancer.Plasma SPARC acts as a mediator in this process,suggesting that circulating eosinophil count and plasma SPARC have the potential to become early clinical indicators and therapeutic tar-gets for gastric cancer.The Mendelian randomization method effectively mitigates biases stemming from reverse causality and psychosocial factors.Nevertheless,additional research is imperative to validate its underlying biological mechanisms.