背景:许多荟萃分析和临床研究表明,免疫细胞的亚型与皮肤癌的发展有关,但目前尚不清楚这种关联是因果的还是有偏见的。与传统研究相比,孟德尔随机化(MR)分析减少了混杂因素的影响,并提高了结果的准确性。因此,为了检查各种免疫细胞与皮肤癌之间的因果关系,本研究采用双样本MR。
方法:本研究使用双样本孟德尔随机化(MR)方法评估了731免疫细胞特征与皮肤癌之间的因果关系。使用多种MR方法来偏倚并得出工具变量与结果之间因果关系的可靠估计。综合敏感性分析用于验证稳定性,结果的异质性和水平多重性。
结果:我们发现不同类型的免疫细胞与皮肤癌疾病之间存在潜在的因果关系。具体来说,一种类型的免疫细胞可能导致皮肤恶性黑色素瘤(MM),八种不同类型的免疫细胞可能导致基底细胞癌(BCC),四种不同类型的免疫细胞可能导致光化性角化病(AK),并且没有发现不同类型的免疫细胞与鳞状细胞癌(SCC)有潜在的因果关系,所有结果都具有稳定性。
结论:这项研究通过遗传手段证明了免疫细胞与皮肤癌疾病之间的紧密联系,这丰富了当前有关免疫细胞在皮肤癌中的作用的知识,也有助于从免疫学角度设计治疗策略。
BACKGROUND: Numerous meta-analyses and clinical studies have shown that subtypes of immune cells are associated with the development of skin cancer, but it is not clear whether this association is causal or biased. Mendelian randomization (MR) analysis reduces the effect of confounding factors and improves the accuracy of the results when compared to traditional studies. Thus, in order to examine the causal relationship between various immune cell and skin cancer, this study employs two-sample MR.
METHODS: This study assesses the causal association between 731 immune cell characteristics and skin cancer using a two-sample Mendel randomization (MR) methodology. Multiple MR methods were used to bias and to derive reliable estimates of causality between instrumental variables and outcomes. Comprehensive sensitivity analyses were used to validate the stability, heterogeneity and horizontal multiplicity of the results.
RESULTS: We discovered that potential causal relationships between different types of immune cells and skin cancer disease. Specifically, one type of immune cell as potentially causal to malignant melanoma of skin (MM), eight different types of immune cells as potentially causal to basal cell carcinoma (BCC), four different types of immune cells as potentially causal to actinic keratosis (AK), and no different types of immune cells were found to have a potential causal association with squamous cell carcinoma(SCC), with stability in all of the results.
CONCLUSIONS: This study demonstrates the close connection between immune cells and skin cancer disease by genetic means, which enriches the current knowledge about the role of immune cells in skin cancer and also contributes to the design of therapeutic strategies from an immunological perspective.