Department of Medicine, Dan L. Duncan Comprehensive Cancer Center, Baylor College of Medicine, One Baylor Plaza, Mailstop BCM305, Houston, TX, 77030, USA.
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
J Neurooncol. 2018 Jan;136(1):33-39. doi: 10.1007/s11060-017-2622-6. Epub 2017 Sep 30.
Immune cells of myeloid origin, including microglia, macrophages, and myeloid-derived suppressor cells adopt immunosuppressive phenotypes that support gliomagenesis. Here, we tested an a priori hypothesis that single nucleotide polymorphisms (SNPs) in genes related to glioma-associated myeloid cell regulation and function are also associated with patient survival after glioma diagnosis. Subjects for this study were 992 glioma patients treated at The University of Texas MD Anderson Cancer Center in Houston, Texas between 1992 and 2008. Haplotype-tagging SNPs in 91 myeloid-associated genes were analyzed for association with survival by Cox regression. Individual SNP- and gene-based tests were performed separately in glioblastoma (WHO grade IV, n = 511) and lower-grade glioma (WHO grade II-III, n = 481) groups. After adjustment for multiple testing, no myeloid-associated gene variants were significantly associated with survival in glioblastoma. Two SNPs, rs147960238 in CD163 (p = 2.2 × 10) and rs17138945 in MET (p = 5.6 × 10) were significantly associated with survival of patients with lower-grade glioma. However, these associations were not confirmed in an independent analysis of 563 lower-grade glioma cases from the University of California at San Francisco Adult Glioma Study (p = 0.65 and p = 0.41, respectively). The results of this study do not support a role for inherited polymorphisms in myeloid-associated genes in affecting survival of patients diagnosed with glioblastoma or lower-grade glioma.
髓系来源的免疫细胞,包括小胶质细胞、巨噬细胞和髓系来源的抑制性细胞,会呈现出免疫抑制表型,从而支持神经胶质瘤的发生。在这里,我们检验了一个先验假设,即与胶质瘤相关的髓系细胞调控和功能相关的基因中的单核苷酸多态性(SNP)也与胶质瘤诊断后患者的生存有关。本研究的对象是 1992 年至 2008 年期间在德克萨斯大学 MD 安德森癌症中心接受治疗的 992 名胶质瘤患者。在 Cox 回归分析中,对 91 个与髓系相关的基因中的单倍型标签 SNP 与生存进行了关联分析。在胶质母细胞瘤(WHO 分级 IV,n=511)和低级别胶质瘤(WHO 分级 II-III,n=481)组中分别进行了基于单核苷酸多态性和基因的测试。在进行多重检验调整后,没有与髓系相关的基因变异与胶质母细胞瘤的生存显著相关。两个 SNP,CD163 中的 rs147960238(p=2.2×10)和 MET 中的 rs17138945(p=5.6×10)与低级别胶质瘤患者的生存显著相关。然而,在加利福尼亚大学旧金山分校成人神经胶质瘤研究的 563 例低级别神经胶质瘤病例的独立分析中,这些关联未得到证实(p=0.65 和 p=0.41)。这项研究的结果不支持遗传多态性在髓系相关基因中对诊断为胶质母细胞瘤或低级别胶质瘤的患者的生存产生影响。