研究动态
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基因组尺度甲基化分析鉴定出与膀胱癌预后相关的免疫特征和年龄加速度关联。

Genome-scale methylation analysis identifies immune profiles and age acceleration associations with bladder cancer outcomes.

发表日期:2023 Aug 01
作者: Ji-Qing Chen, Lucas A Salas, John K Wiencke, Devin C Koestler, Annette M Molinaro, Angeline S Andrew, John D Seigne, Margaret R Karagas, Karl T Kelsey, Brock C Christensen
来源: Immunity & Ageing

摘要:

免疫特征与膀胱癌预后相关,并可能在预后临床应用中发挥作用。然而,详细的免疫细胞亚型与患者结局的关联仍未被充分探讨,并且可能为更好地管理膀胱癌复发和生存提供关键的预后信息。使用Illumina HumanMethylationEPIC芯片测量了膀胱癌病例外周血DNA甲基化。扩展细胞类型分解法定量了十二种免疫细胞类型的比例,包括记忆、纯真T和B细胞以及粒细胞亚型。DNA甲基化钟确定了生物年龄。Cox比例风险模型检测了免疫细胞组合和年龄加速与膀胱癌结局的关联。partDSA算法通过临床变量和免疫细胞组合判断10年总生存组别,并使用DNA甲基化数据应用半监督递归分割混合模型识别10年总生存的分类器。高CD8T记忆细胞比例与更好的总生存相关(HR=0.95,95% CI=0.93-0.98),而较高的NLR(HR=1.36,95% CI=1.23-1.50),CD8T纯真细胞(HR=1.21,95% CI=1.04-1.41),嗜中性粒细胞(HR=1.04,95% CI=1.03-1.06)比例和年龄加速(HR=1.06,95% CI=1.03-1.08)与膀胱癌患者的总生存较差相关。partDSA和SS-RPMM将对象划分为五组,其总生存率有显著差异。我们发现免疫细胞亚型和年龄加速与膀胱癌结局相关。该研究结果表明,膀胱癌结局与特定甲基化衍生的免疫细胞类型比例和年龄加速相关,这些因素可能是潜在的预后生物标志物。
Immune profiles have been associated with bladder cancer outcomes and may have clinical applications for prognosis. However, associations of detailed immune cell subtypes with patient outcomes remain underexplored and may contribute crucial prognostic information for better managing bladder cancer recurrence and survival.Bladder cancer case peripheral blood DNA methylation was measured using the Illumina HumanMethylationEPIC array. Extended cell-type deconvolution quantified twelve immune cell-type proportions, including memory, naïve T and B cells, and granulocyte subtypes. DNA methylation clocks determined biological age. Cox proportional hazard models tested associations of immune cell profiles and age acceleration with bladder cancer outcomes. The partDSA algorithm discriminated 10-year overall survival groups from clinical variables and immune cell profiles, and a semi-supervised recursively partitioned mixture model with DNA methylation data was applied to identify a classifier for 10-year overall survival.Higher CD8T memory cell proportions were associated with better overall survival (HR=0.95, 95% CI=0.93-0.98), while higher NLR (HR=1.36, 95% CI=1.23-1.50), CD8T naïve (HR=1.21, 95% CI=1.04-1.41), neutrophil (HR=1.04, 95% CI=1.03-1.06) proportions, and age acceleration (HR =1.06, 95% CI=1.03-1.08) were associated with worse overall survival in bladder cancer patients. partDSA and SS-RPMM classified five groups of subjects with significant differences in overall survival.We identified associations between immune cell subtypes and age acceleration with bladder cancer outcomes.The findings of this study suggest that bladder cancer outcomes are associated with specific methylation-derived immune cell-type proportions and age acceleration, and these factors could be potential prognostic biomarkers.