Zhou Qianhui, Liang Yanchao, Chen Xun, Qi Siwei, Wei Lanlan
Department of Respiratory and Critical Care Medicine, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, 412000, Hunan, China.
Department of Hepatobiliary Surgery, Zhuzhou Hospital Affiliated to Xiangya School of Medicine, Central South University, Zhuzhou, 412000, Hunan, China.
Discov Oncol. 2024 Nov 30;15(1):731. doi: 10.1007/s12672-024-01637-2.
Lung cancer (LC) is the leading cause of cancer-related deaths in China, with its incidence and mortality rates rising annually. Various studies have demonstrated disparities in immune cell counts and profiles between LC patients and healthy individuals. However, the existence of a causal link remains largely uncertain. To explore the potential causal association between immune cells and LC risk, a Mendelian randomization (MR) approach was employed.
Employing immune cell genome-wide association study (GWAS) data from a public database (n = 731 subjects) and Lung Cancer Genome Research Consortium's GWAS dataset (n = 492,803 participants), unconventional genetic loci remarkably associated with the significant abundance of 731 types of immune cells were extracted according to preset threshold points as instrumental variables. The primarily analytical strategy involved the inverse variance weighting (IVW) method, with the effect size estimates expressed as odds ratio (OR) and 95% CI. The robustness of the findings was assessed through a leave-one-out sensitivity analysis, heterogeneity test, horizontal gene pleiotropy test, MR-PRESSO and MR-Egger.
The MR analysis identified a significant association between 18 distinct immune cell types and lung cancer risk. MR analysis revealed that 7 types of immune cells, including CD20 on IgD - CD38 - B cell, CD20 on switched memory B cell, IgD on IgD + CD24 + B cell, BAFF - R on IgD - CD38 + B cell, CD39 + resting CD4 regulatory T cell Absolute Count, CD127 on CD45RA + CD4 + T cell, CD8 on Effector Memory CD8 + T cell, displayed a protective effect against lung cancer development. Conversely, 11 other immune cells populations were positive associated with an increased lung cancer risk. In contrast, reverse MR analysis indicated that the lung cancer risk was linked to 11 immune cells, with 2 types of immune cells (CD25 on IgD - CD27 - B cell, CD4 + T cell %leukocyte) showing a are positive correlation with cancer development, whereas 9 types of immune cells appeared to be inversely regulated. These findings collectively imply that specific immune cell populations may play critical roles in either promoting or suppressing the initiation and progression of lung cancer.
The findings of this study offer fresh insights into the underlying biological mechanisms governing lung cancer development, thereby opening new avenues for future research in the domain of LC. The identification of specific immune cell subsets with protective or promoting roles provides crucial leads for preventive and therapeutic strategies. These insights have the potential to enhance early detection methods and inform the development of more effective treatment approaches, ultimately benefiting patient outcomes and improving the overall management of lung cancer.
肺癌是中国癌症相关死亡的主要原因，其发病率和死亡率逐年上升。各种研究表明，肺癌患者与健康个体之间的免疫细胞计数和特征存在差异。然而，因果关系的存在在很大程度上仍不确定。为了探索免疫细胞与肺癌风险之间的潜在因果关联，采用了孟德尔随机化（MR）方法。
利用来自公共数据库（n = 731名受试者）的免疫细胞全基因组关联研究（GWAS）数据和肺癌基因组研究联盟的GWAS数据集（n = 492,803名参与者），根据预设阈值点提取与731种免疫细胞的显著丰度显著相关的非常规遗传位点作为工具变量。主要分析策略采用逆方差加权（IVW）方法，效应大小估计值以比值比（OR）和95%置信区间表示。通过留一法敏感性分析、异质性检验、水平基因多效性检验、MR-PRESSO和MR-Egger评估研究结果的稳健性。
MR分析确定了18种不同免疫细胞类型与肺癌风险之间存在显著关联。MR分析显示，7种免疫细胞，包括IgD-CD38-B细胞上的CD20、转换记忆B细胞上的CD20、IgD+CD24+B细胞上的IgD、IgD-CD38+B细胞上的BAFF-R、CD39+静息CD4调节性T细胞绝对计数、CD45RA+CD4+T细胞上的CD127、效应记忆CD8+T细胞上的CD8，对肺癌发展具有保护作用。相反，其他11种免疫细胞群体与肺癌风险增加呈正相关。相比之下，反向MR分析表明，肺癌风险与11种免疫细胞有关，其中2种免疫细胞（IgD-CD27-B细胞上的CD25、CD4+T细胞%白细胞）与癌症发展呈正相关，而9种免疫细胞似乎受到反向调节。这些发现共同表明，特定的免疫细胞群体可能在促进或抑制肺癌的发生和发展中起关键作用。
本研究结果为肺癌发生发展的潜在生物学机制提供了新的见解，从而为肺癌领域的未来研究开辟了新途径。识别具有保护或促进作用的特定免疫细胞亚群为预防和治疗策略提供了关键线索。这些见解有可能加强早期检测方法，并为开发更有效的治疗方法提供信息，最终改善患者预后并提高肺癌的整体管理水平。
