The Second Affiliated Hospital, Yuying Children's Hospital, Wenzhou Medical University, 109 West Xueyuan Road, Lucheng District, Zhejiang, 325007, Wenzhou, PR China.
Department of Children's Respiration Disease, The Second Affiliated Hospital and Yuying Children's Hospital, Wenzhou Medical University, 109 West Xueyuan Road, Lucheng District, 325027, Wenzhou, Zhejiang, PR China.
BMC Cancer. 2024 Feb 26;24(1):270. doi: 10.1186/s12885-024-12014-1.
Previous studies have observed a link between immunophenotypes and lung cancer, both of which are closely associated with genetic factors. However, the causal relationship between them remains unclear.
Bidirectional Mendelian randomization (MR) was performed on publicly available genome-wide association study (GWAS) summary statistics to analyze the causal relationships between 731 immunophenotypes and lung cancer. Sensitivity analyses were conducted to verify the robustness, heterogeneity, and potential horizontal pleiotropy of our findings.
Following Bonferroni adjustment, CD14 CD16 monocyte (OR = 0.930, 95%CI 0.900-0.960, P = 8.648 × 10, P = 0.006) and CD27 on CD24 CD27 B cells (OR = 1.036, 95%CI 1.020-1.053, P = 1.595 × 10 - 5, P = 0.012) were identified as having a causal role in lung cancer via the inverse variance weighted (IVW) method. At a more relaxed threshold, CD27 on IgD CD24 B cell (OR = 1.035, 95%CI 1.017-1.053, P = 8.666 × 10, P = 0.063) and CD27 on switched memory B cell (OR = 1.037, 95%CI 1.018-1.056, P = 1.154 × 10, P = 0.084) were further identified. No statistically significant effects of lung cancer on immunophenotypes were found.
The elevated level of CD14 CD16 monocytes was a protective factor against lung cancer. Conversely, CD27 on CD24 CD27 B cell was a risk factor. CD27 on class-switched memory B cells and IgD CD24 B cells were potential risk factors for lung cancer. This research enhanced our comprehension of the interplay between immune responses and lung cancer risk. Additionally, these findings offer valuable perspectives for the development of immunologically oriented therapeutic strategies.
先前的研究已经观察到免疫表型与肺癌之间存在关联，两者都与遗传因素密切相关。然而，它们之间的因果关系尚不清楚。
利用公开的全基因组关联研究（GWAS）汇总统计数据，采用双向孟德尔随机化（MR）分析 731 种免疫表型与肺癌之间的因果关系。进行敏感性分析以验证我们研究结果的稳健性、异质性和潜在的水平多效性。
经 Bonferroni 调整后，CD14 CD16 单核细胞（OR=0.930，95%CI 0.900-0.960，P=8.648×10-8，P=0.006）和 CD27 阳性 CD24 CD27 B 细胞（OR=1.036，95%CI 1.020-1.053，P=1.595×10-5，P=0.012）通过逆方差加权（IVW）法被确定为与肺癌具有因果关系。在更为宽松的阈值下，IgD CD24 B 细胞上的 CD27（OR=1.035，95%CI 1.017-1.053，P=8.666×10-6，P=0.063）和转换记忆 B 细胞上的 CD27（OR=1.037，95%CI 1.018-1.056，P=1.154×10-5，P=0.084）也被进一步确定。未发现肺癌对免疫表型有统计学显著影响。
CD14 CD16 单核细胞水平升高是肺癌的保护因素。相反，CD27 阳性 CD24 CD27 B 细胞是肺癌的危险因素。转换记忆 B 细胞和 IgD CD24 B 细胞上的 CD27 可能是肺癌的潜在危险因素。这项研究增强了我们对免疫反应与肺癌风险之间相互作用的理解。此外，这些发现为免疫导向治疗策略的发展提供了有价值的视角。
