Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
Epigenome-wide gene-age interaction analysis reveals reversed effects of PRODH DNA methylation on survival between young and elderly early-stage NSCLC patients
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全表观基因组基因年龄相互作用分析揭示 PRODH DNA 甲基化对年轻和老年早期 NSCLC 患者生存的逆转影响
DOI：
10.18632/aging.103284
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发表时间：
2020-06-15
期刊：
影响因子：
5.2
通讯作者：
Christiani, David C.
中科院分区：
文献类型：
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作者：
Chen, Chao;Wei, Yongyue;Christiani, David C.
DNA甲基化在衰老过程中发生变化，但目前尚不清楚DNA甲基化对肺癌生存率的影响是否随年龄而变化。这种效应可能会降低预测准确性和治疗效果。我们对来自5个队列的1,230例早期肺腺癌患者进行了甲基化-年龄相互作用分析。使用考克斯比例风险模型研究肺腺癌和鳞状细胞癌患者的甲基化-年龄相互作用，并在验证阶段进一步证实。我们鉴定了一种腺癌特异性CpG探针，cg 14326354（PRODH），其作用随年龄显著改变（HR相互作用= 0.989; 95%CI：0.986-0.994; P = 9.18x10-7）。根据95%CI标准的边界分类，年轻和老年患者的低甲基化效应逆转（HRyoung = 2.44; 95%CI：1.26-4.72; P = 8.34x10-3; HRerderly = 0.58; 95%CI：0.42-0.82; P = 1.67x10-3）。此外，低cg 14326354（PRODH）甲基化与老年之间存在拮抗性相互作用（HR相互作用= 0.21; 95% CI：0.11-0.40; P = 2.20 × 10 -6）。总之，cg 14326354 PRODH的低甲基化可能有利于老年肺腺癌患者的生存，为年龄特异性预测和潜在的药物靶向提供了新的见解。
DNA methylation changes during aging, but it remains unclear whether the effect of DNA methylation on lung cancer survival varies with age. Such an effect could decrease prediction accuracy and treatment efficacy. We performed a methylation-age interaction analysis using 1,230 early-stage lung adenocarcinoma patients from five cohorts. A Cox proportional hazards model was used to investigate lung adenocarcinoma and squamous cell carcinoma patients for methylation-age interactions, which were further confirmed in a validation phase. We identified one adenocarcinoma-specific CpG probe, cg14326354(PRODH), with effects significantly modified by age (HRinteraction = 0.989; 95% CI: 0.986-0.994; P = 9.18x10-7). The effect of low methylation was reversed for young and elderly patients categorized by the boundary of 95% CI standard (HRyoung = 2.44; 95% CI: 1.26-4.72; P = 8.34x10-3; HRelderly = 0.58; 95% CI: 0.42-0.82; P = 1.67x10-3). Moreover, there was an antagonistic interaction between low cg14326354(PRODH) methylation and elderly age (HRinteraction = 0.21; 95% CI: 0.11-0.40; P = 2.20x10-6). In summary, low methylation of cg14326354PRODH might benefit survival of elderly lung adenocarcinoma patients, providing new insight to age-specific prediction and potential drug targeting.