宫颈癌与免疫细胞因果关系的两样本孟德尔随机化研究

Causal Association Between Immune Cells and Cervical Cancer:A Two-Sample Mendelian Randomization Study

目的采用双样本孟德尔随机化分析方法探究宫颈癌和免疫细胞之间的因果关系。方法从GWAS Catalog数据库中获取731种外周血免疫表型的数据集作为暴露因素数据,从FinnGen数据库获取宫颈癌的GWAS数据集作为结局数据。使用逆方差加权法、MR Egger法、加权中位数法和加权模式法进行分析。为保证分析结果的可靠性,还进行了敏感性分析和反向孟德尔随机化分析,以排除偏倚和反向因果关系。MR Steiger方向性检验用于确定免疫细胞和宫颈癌之间的反向因果关系。结果本研究共筛选到71个免疫细胞亚型与宫颈癌存在相关性,其中31个细胞亚型与宫颈癌高度相关。大部分B细胞是宫颈癌的保护因子。B细胞活化因子受体(BAFF-R)是本研究中最常见的表达分子,在多种B细胞亚型上表达;IgD+CD38+B细胞上CD20的表达水平(OR=1.887,95%CI:1.078~3.306,P=0.026)是宫颈癌发病的危险因素。在树突状细胞分组中,CD123在浆细胞样树突状细胞(OR=2.48,95%CI:1.229~5.003,P=0.011)、CD62L+浆细胞样树突状细胞(OR=2.5,95%CI:1.231~5.077,P=0.011)、CD80在浆细胞样树突状细胞(OR=2.62,95%CI:1.244~5.515,P=0.011)和CD62L+浆细胞样树突状细胞(OR=2.641,95%CI:1.246~5.596,P=0.011)上的表达与宫颈癌发病率呈正相关。反向MR分析结果表明,本研究中所有妇科癌症对免疫细胞的影响差异无统计学意义。结论本研究提出了免疫细胞和宫颈癌之间的遗传预测因果关系,在临床实践中,宫颈癌患者需重视外周血免疫细胞的筛查。

Objective To investigate potential causative associations between immunophenotype traits and cervical cancer by using two-sample Mendelian randomization(MR)analysis.Methods The genetic instrumental variables(IVs)of 731 immunophenotypes of peripheral blood were obtained from the GWAS Catalog database.The GWAS summary data of cervical cancer were obtained from FinnGen database.The inverse-variance weighted(IVW),weighted mode,weighted median,and MR Egger methods were used for evaluations.The sensitivity analysis and reverse Mendelian randomization analysis were conducted to eliminate bias and reverse causality.The MR Steiger directionality test was further used to ascertain the reverse causal relationship between immune cells and cervical cancer.Results A total of 71 immune cell subtypes associated with cervical cancer were identified,of which 31 had a strong association.The majority of the B cell panel was protective factors for cervical cancer.B-cell activating factor receptor(BAFF-R)was the most frequently expressed molecule in this analysis.It is expressed on several B cell subtypes.The CD20 on IgD+CD38+B cell(OR=1.887,95%CI:1.078-3.306,P=0.026)is the risk factor for cervical cancer.In cDC panels,the CD123 expression on plasmacytoid dendritic cell(OR=2.48,95%CI:1.229-5.003,P=0.011),CD123 expression on CD62L+plasmacytoid dendritic cell(OR=2.5,95%CI:1.231-5.077,P=0.011),CD80 expression on plasmacytoid dendritic cell(OR=2.62,95%CI:1.244-5.515,P=0.011),and CD80 expression on CD62L+plasmacytoid dendritic cell(OR=2.641,95%CI:1.246-5.596,P=0.011)were positively associated with the incidence of cervical cancer.All gynecological cancers in this study have no statistically significant effect on immune cells,according to reverse MR analysis.Conclusion This study emphasized the genetically predicted causality between immune cells and cervical cancer.In clinical practice,it is important to pay attention to the screening of peripheral blood immune cells for patients with cervical cancer.