观察性研究已经发现循环炎症蛋白和免疫细胞对癌症进展的双重影响。然而，在皮肤源性肿瘤恶化中的具体作用机制尚未阐明。因此，本研究旨在探讨循环炎症因子与基底细胞癌（BCC）、皮肤恶性黑色素瘤（SKCM）和皮肤鳞状细胞癌（cSCC）之间的因果关系是否受到免疫细胞的调节。本研究采用了两种方法：孟德尔随机化 (TSMR) 样本方法从遗传学角度研究 91 种循环炎症因子与三种流行类型皮肤癌之间的因果关系。贝叶斯加权孟德尔随机化 (BWMR) 还用于验证相关性，并使用反向 MR 来评估反向关系。随后进行敏感性分析以限制异质性和多效性的影响。最后，利用两步孟德尔随机化（两步MR）方法来确定特定免疫细胞特征在循环炎症因子与BCC、SKCM和cSCC之间的因果通路中的中介作用。逆方差加权（IVW）方法和贝叶斯加权算法共同确定了与 BCC、SKCM 和 cSCC 因果相关的 9 种炎症因子。 Cochran's Q 检验、孟德尔随机化多效性残差和和离群值 (MR-PRESSO) 以及 MR-Egger 截距的结果不具有统计显着性 (p < 0.05)。此外，CD4 CD8dim T 细胞白细胞百分比、CD4-CD8-自然杀伤 T 细胞百分比和 IgD-CD38-B 细胞上的 CD20 介导的 FIt3L、CCL4 和 OSM 比例分别为 9.26%、8.96% 和 10.16%免疫细胞水平可能在循环炎症蛋白和皮肤源性恶化肿瘤之间的调节过程中发挥作用。这一发现为深入探索皮肤恶性肿瘤提供了新的视角。© 2024 作者。约翰·威利 (John Wiley) 出版的皮肤研究与技术

Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous-origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells.This study employed the Two-Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two-step Mendelian Randomization (two-step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC.The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4-CD8-Natural Killer T %T cell, and CD20 on IgD-CD38-B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively.Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous-origin exacerbated tumors. This finding offers a new perspective for the in-depth exploration of cutaneous malignancies.© 2024 The Author(s). Skin Research and Technology published by John Wiley & Sons Ltd.