Hou Shiqiang, Jin Chunjing, Shi Beitian, Chen Yinan, Lin Ning
Department of Neurosurgery, The Affiliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou, China.
Laboratory Medicine Center, The Affiliated Chuzhou Hospital of Anhui Medical University, The First People's Hospital of Chuzhou, Chuzhou, China.
J Cancer. 2025 Jan 1;16(1):171-181. doi: 10.7150/jca.100519. eCollection 2025.
Glioblastoma (GBM) and immunology are closely related, but its mechanism remains unclear. This study aimed to observe the causal inference between GBM and various immune cells by bidirectional Mendelian randomization (MR) analysis. We used immune cell and GBM data from the GWAS database. A total of 731 immunophenotypes, including four trait types and seven panels. For bidirectional MR analysis, Inverse Variance Weighted and False Discovery Rate (FDR) were both employed. Sensitivity analysis was also performed to make sure the results were reliable. According to FDR, seven immunophenotypes associated with GBM risk: CD33br HLA DR+ AC (FDR = 0.009), CD38 on PB/PC (FDR = 0.046), CD66b on CD66b++ myeloid cell (FDR = 0.019), CD3 on CD39+ resting Treg (FDR = 0.009), HVEM on CM CD8br (FDR = 0.050), CD45 on CD33br HLA DR+ CD14dim (FDR = 0.027), and CD86 on CD62L+ myeloid DC (FDR = 0.048). In reverse MR analysis, GBM was found to be strongly associated with nine immunophenotypes based on FDR: BAFF-R on CD24+ CD27+ (FDR = 0.033), BAFF-R on IgD+ CD38- (FDR = 0.036), BAFF-R on IgD-CD38br (FDR = 0.039), BAFF-R on unsw mem (FDR = 0.048), BAFF-R on CD20- (FDR=0.012), HVEM on EM CD8br (FDR=0.036), CCR2 on myeloid DC (FDR = 0.035), CD45 on CD33-HLA DR+ (FDR = 0.004), and CD34 on HSC (FDR = 0.035). The current study confirmed the causal inference between 16 different immunophenotypes and GBM using genetic tools, providing an important foundation and guide for future immunological research and immunotherapy of GBM.
胶质母细胞瘤（GBM）与免疫学密切相关，但其机制仍不清楚。本研究旨在通过双向孟德尔随机化（MR）分析观察GBM与各种免疫细胞之间的因果推断。我们使用了来自GWAS数据库的免疫细胞和GBM数据。共有731种免疫表型，包括四种特征类型和七个组。对于双向MR分析，采用了逆方差加权法和错误发现率（FDR）。还进行了敏感性分析以确保结果可靠。根据FDR，七种免疫表型与GBM风险相关：CD33br HLA DR + AC（FDR = 0.009）、PB/PC上的CD38（FDR = 0.046）、CD66b ++髓样细胞上的CD66b（FDR = 0.019）、CD39 +静息调节性T细胞上的CD3（FDR = 0.009）、CM CD8br上的HVEM（FDR = 0.050）、CD33br HLA DR + CD14dim上的CD45（FDR = 0.027）以及CD62L +髓样树突状细胞上的CD86（FDR = 0.048）。在反向MR分析中，基于FDR发现GBM与九种免疫表型密切相关：CD24 + CD27 +上的BAFF-R（FDR = 0.033）、IgD + CD38 -上的BAFF-R（FDR = 0.036）、IgD-CD38br上的BAFF-R（FDR = 0.039）、未转换记忆细胞上的BAFF-R（FDR = 0.048）、CD20 -上的BAFF-R（FDR = 0.012）、EM CD8br上的HVEM（FDR = 0.036）、髓样树突状细胞上的CCR2（FDR = 0.035）、CD33 - HLA DR +上的CD45（FDR = 0.004）以及造血干细胞上的CD34（FDR = 0.035）。本研究使用遗传工具证实了16种不同免疫表型与GBM之间的因果推断，为未来GBM的免疫学研究和免疫治疗提供了重要基础和指导。
