宫颈癌与免疫细胞表型的孟德尔随机化研究
Mendelian Randomization Study on Cervical Cancer and Immune Cell Phenotypes
【 】目的：采用两样本孟德尔随机化(Two Sample Mendelian Randomization，MR)分析方法，探究731种免疫细胞表型与宫颈癌的因果关系。方法： 使用全基因组关联研究（Genome-Wide Association Studies，GWAS），采用逆方差加权法（Inverse Variance Weighting, IVW）、MR-Egger回归法(MR-Egger Regression, MR-Egger)、加权中位数法（Weighted Median Estimation, WME）、简易模式法(Simplified Mode，SM)和加权模式法(Weighted Mode，WM)进行MR分析，同时采用敏感性分析对异质性及水平多效性进行质控。结果：以IVW作为主要分析方法 (PIVW < 0.01)，且5种MR分析方法结果方向均一致，共鉴定出5种免疫细胞表型与宫颈癌可能存在因果关联，其中3种免疫细胞表型：中央记忆阶段的CD4+ T细胞在所有CD4+ T细胞中的比例（Relative count of Central Memory CD4+ T cells in all CD4+ T cells CM CD4+%CD4+，ORIVW=0.804，95% CI:0.685-0.943, PIVW=0.0074 ）, 幼稚阶段的CD8高亮T细胞的绝对数（Absolute count of Naive CD8 Bright+ T cell Naive CD8br AC, ORIVW=0.493，95% CI:0.359-0.676, PIVW=0.00001）及CD45在未成熟的髓源抑制细胞上的中位荧光强度 (Median fluorescence intensities of CD45 on Immature Myeloid-Derived Suppressor Cells CD45 on Im MDSC, ORIVW=0.746，95% CI: 0.609-0.914, PIVW=0.0048）, 与宫颈癌风险呈正相关；2种免疫细胞表型：IgD 在IgD+CD38- 未转化初始型记忆B 细胞上的中位荧光强度 （Median fluorescence intensities of IgD on IgD+ CD38- unswitched memory B cell IgD on IgD+ CD38- unsw mem， ORIVW=1.393，95% CI: 1.148 -1.69, PIVW=0.00078）及CD3在终末分化型的CD8高亮T细胞上的中位荧光强度 (Median fluorescence intensities of CD3 on Terminally Differentiated CD8+ T cell CD3 on TD CD8br， ORIVW=1.267，95% CI: 1.082 -1.483, PIVW=0.0033），与宫颈癌风险呈负相关。结论： 本研究通过遗传学手段筛选出了5种与宫颈癌风险密切相关的免疫细胞表型，为今后宫颈癌的早期预防和开发新的免疫疗法提供了新的参考。
【 】Objective: This study aims to explore the causal relationships between 731 immune cell phenotypes and cervical cancer using a two-sample MR (Mendelian randomization) analysis. Methods: Utilizing results from GWAS (Genome-Wide Association Studies), we conducted MR analysis using IVW (Inverse Variance Weighted) method as the primary approach, along with MR-Egger regression, WME (Weighted Median Estimation), SM(simple mode), and WM(weighted mode) methods. Sensitivity analyses were performed to assess heterogeneity and horizontal pleiotropy. Results: Using IVW as the primary analytical method (PIVW<0.01) and ensuring consistency in the direction of results across all five MR methods, we identified five immune cell phenotypes potentially causally associated with cervical cancer. Among these, three immune cell phenotypes, CM CD4+%CD4+ T cell (ORIVW=0.804, 95% CI:0.685-0.943, PIVW=0.0074), Naive CD8br T cell AC (ORIVW=0.493, 95% CI:0.359-0.676, PIVW=0.00001), and CD45 on Im MDSC (ORIVW=0.746, 95% CI:0.609-0.914, PIVW=0.0048), were positively associated with cervical cancer risk, while two immune cell phenotypes, IgD on IgD+ CD38- unswitched memory (ORIVW=1.393, 95% CI:1.148-1.69, PIVW=0.00078) and CD3 on TD CD8br (ORIVW=1.267, 95% CI:1.082-1.483, PIVW=0.0033), were negatively associated with cervical cancer risk. Conclusion: This study identifies five immune cell phenotypes closely related to cervical cancer risk through genetic analysis, providing new insights for early prevention and the development of novel immunotherapies for cervical cancer.
王光演、南霜、郑靖宇
肿瘤学医学研究方法基础医学
［］孟德尔随机化宫颈癌免疫细胞全基因组关联研究
Mendelian randomizationCervical cancerImmune cellsGenome-wide association study
王光演,南霜,郑靖宇.宫颈癌与免疫细胞表型的孟德尔随机化研究[EB/OL].(2024-12-07)[2025-08-22].https://www.biomedrxiv.org.cn/article/doi/bmr.202412.00050.点此复制
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