年龄和血液免疫因素的相互作用与胶质瘤生存的无创预测。
Interactions of Age and Blood Immune Factors and Noninvasive Prediction of Glioma Survival.
机构信息
Department of Neurological Surgery, University of California San Francisco, San Francisco, CA, USA.
Department of Epidemiology and Biostatistics, University of California San Francisco, San Francisco, CA, USA.
出版信息
J Natl Cancer Inst. 2022 Mar 8;114(3):446-457. doi: 10.1093/jnci/djab195.
BACKGROUND
Tumor-based classification of human glioma portends patient prognosis, but considerable unexplained survival variability remains. Host factors (eg, age) also strongly influence survival times, partly reflecting a compromised immune system. How blood epigenetic measures of immune characteristics and age augment molecular classifications in glioma survival has not been investigated. We assess the prognostic impact of immune cell fractions and epigenetic age in archived blood across glioma molecular subtypes for the first time.
METHODS
We evaluated immune cell fractions and epigenetic age in archived blood from the University of California San Francisco Adult Glioma Study, which included a training set of 197 patients with IDH-wild type, 1p19q intact, TERT wild type (IDH/1p19q/TERT-WT) glioma, an evaluation set of 350 patients with other subtypes of glioma, and 454 patients without glioma.
RESULTS
IDH/1p19q/TERT-WT patients had lower lymphocyte fractions (CD4+ T, CD8+ T, natural killer, and B cells) and higher neutrophil fractions than people without glioma. Recursive partitioning analysis delineated 4 statistically significantly different survival groups for patients with IDH/1p19q/TERT-WT based on an interaction between chronological age and 2 blood immune factors, CD4+ T cells, and neutrophils. Median overall survival ranged from 0.76 years (95% confidence interval = 0.55-0.99) for the worst survival group (n = 28) to 9.72 years (95% confidence interval = 6.18 to not available) for the best (n = 33). The recursive partitioning analysis also statistically significantly delineated 4 risk groups in patients with other glioma subtypes.
CONCLUSIONS
The delineation of different survival groups in the training and evaluation sets based on an interaction between chronological age and blood immune characteristics suggests that common host immune factors among different glioma types may affect survival. The ability of DNA methylation-based markers of immune status to capture diverse, clinically relevant information may facilitate noninvasive, personalized patient evaluation in the neuro-oncology clinic.
背景
基于肿瘤的人类神经胶质瘤分类预示着患者的预后，但仍存在大量无法解释的生存差异。宿主因素（如年龄）也强烈影响生存时间，部分原因是免疫系统受损。血液中免疫特征和年龄的表观遗传测量如何增强神经胶质瘤生存的分子分类尚未得到研究。我们首次评估了免疫细胞分数和表观遗传年龄在神经胶质瘤分子亚型中存档血液中的预后影响。
方法
我们评估了加利福尼亚大学旧金山成人神经胶质瘤研究中存档血液中的免疫细胞分数和表观遗传年龄，该研究包括一个 IDH 野生型、1p19q 完整、TERT 野生型（IDH/1p19q/TERT-WT）神经胶质瘤患者的训练集（197 例）、一个其他神经胶质瘤亚型患者的验证集（350 例）和 454 例无神经胶质瘤患者的数据集。
结果
IDH/1p19q/TERT-WT 患者的淋巴细胞分数（CD4+ T、CD8+ T、自然杀伤细胞和 B 细胞）低于无神经胶质瘤患者，中性粒细胞分数高于无神经胶质瘤患者。递归分区分析根据年龄和血液免疫因素（CD4+ T 细胞和中性粒细胞）之间的相互作用，为 IDH/1p19q/TERT-WT 患者划定了 4 个统计学上不同的生存组。IDH/1p19q/TERT-WT 患者中最差生存组（n=28）的中位总生存期范围为 0.76 年（95%置信区间为 0.55-0.99），最好的生存组（n=33）为 9.72 年（95%置信区间为 6.18-无）。递归分区分析还在其他神经胶质瘤亚型患者中划定了 4 个风险组。
结论
基于年龄和血液免疫特征之间的相互作用，在训练集和验证集中划定不同的生存组表明，不同神经胶质瘤类型之间的常见宿主免疫因素可能影响生存。基于免疫状态的 DNA 甲基化标记的能力可以捕获多样化的、临床相关的信息，这可能有助于在神经肿瘤学临床实践中进行非侵入性的、个性化的患者评估。
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