Department of Thoracic Surgery, Jiangmen Central Hospital, Jiangmen, Guangdong, China.
Department of Breast Cancer Center, Chongqing University Cancer Hospital, Chongqing, China.
Front Immunol. 2024 Jun 19;15:1433299. doi: 10.3389/fimmu.2024.1433299. eCollection 2024.
Previous studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored.
We applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR-Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and identified immunophenotypes, using R software for all statistical calculations.
Our MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (OR =0.885; 95% CI: 0.798-0.983; =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (OR =1.054; 95% CI: 1.010-1.100; =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (OR =0.941; 95% CI: 0.898-0.987; =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (OR =0.958; 95% CI: 0.924-0.992; =0.017) as well as on plasmacytoid dendritic cells (OR =0.958; 95% CI: 0.924-0.992; =0.017) in lung squamous cell carcinoma.
This study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management.
先前的研究强调了免疫细胞在肺癌发展中的关键作用；然而，免疫表型与肺癌之间的直接联系仍未得到充分探索。
我们应用两样本孟德尔随机化（MR）分析，使用遗传变异作为工具来确定暴露对结局的因果影响。这种方法与传统的随机对照试验（RCT）不同，它利用在受孕时随机遗传的遗传变异，从而减少混杂并防止反向因果关系。我们的分析涉及三项全基因组关联研究，使用遗传工具变量（IVs）评估 731 种免疫细胞特征对肺癌的因果影响。我们最初使用标准逆方差加权（IVW）方法，并使用三种补充 MR 技术（MR-Egger、加权中位数和 MR-PRESSO）进一步验证我们的发现，以确保稳健性。我们还进行了 MR-Egger 截距和 Cochrane Q 检验，以评估异质性和多效性。此外，我们还使用 R 软件进行了潜在的因果关系分析，以探索肺癌亚型和鉴定的免疫表型之间的关系。
我们的 MR 分析确定了 106 个与肺癌显著相关的免疫特征。值得注意的是，我们在所有敏感性测试中发现了五个提示性关联（<0.05）：小细胞肺癌中 CD25 在 IgD-CD24-细胞上（OR=0.885；95%CI：0.798-0.983；=0.022）；肺鳞癌中 CD27 在 IgD+CD24+细胞上（OR=1.054；95%CI：1.010-1.100；=0.015）；肺鳞癌中 CCR2 在单核细胞上（OR=0.941；95%CI：0.898-0.987；=0.012）；CD123 在 CD62L+浆细胞样树突状细胞上（OR=0.958；95%CI：0.924-0.992；=0.017）以及浆细胞样树突状细胞上（OR=0.958；95%CI：0.924-0.992；=0.017）。
本研究在免疫细胞与肺癌之间建立了重要的基因组联系，为未来旨在管理肺癌的临床研究提供了坚实的基础。
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