Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC.
Epigenome-wide three-way interaction study identifies a complex pattern between TRIM27, KIAA0226, and smoking associated with overall survival of early-stage NSCLC.
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DOI：
10.1002/1878-0261.13167
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发表时间：
2022-03
影响因子：
6.6
通讯作者：
Christiani DC
中科院分区：
文献类型：
--
作者：
Ji X;Lin L;Fan J;Li Y;Wei Y;Shen S;Su L;Shafer A;Bjaanaes MM;Karlsson A;Planck M;Staaf J;Helland Å;Esteller M;Zhang R;Chen F;Christiani DC
先前已经确定了包含27（cg 05293407 TRIM 27）的三重基序的DNA甲基化与吸烟之间的相互作用，以揭示TRIM 27 DNA甲基化对早期非小细胞肺癌（NSCLC）生存的组织学异质性影响。然而，为了了解NSCLC进展背后的复杂机制，我们搜索了三向相互作用。采用两阶段研究，以确定吸烟包-年（每天吸烟数量×吸烟年数）× cg 05293407 TRIM 27 ×表观基因组范围DNA甲基化CpG探针形式的三向相互作用。在发现阶段鉴别出两种CpG探针，FDR‐q ≤ 0.05，在验证阶段鉴别出P ≤ 0.05：cg 00060500 KIAA 0226和cg 17479956 EXT 2。与仅包含临床信息的预测模型相比，该模型使用更宽松的标准（发现：FDR‐q ≤ 0.10，验证：P ≤ 0.05）添加了42个显著的三向相互作用，显著改善了3年和5年生存期预后预测模型的受试者工作特征曲线下面积（AUC）。本研究明确了多种环境因素和表观遗传因素之间的复杂交互作用，为NSCLC患者提供了治疗靶点。我们进行了一项两阶段设计的表观基因组范围内的三向基因吸烟相互作用研究NSCLC生存率，并确定了两种CpG探针（cg 00060500 KIAA 0226和cg 17479956 EXT 2），以及包年吸烟和cg 05293407 TRIM 27，表现出显著的三向相互作用效应。同时，这些显著的三向相互作用显著改善了3年和5年生存率预后预测模型的受试者工作特征曲线下面积（AUC）。
The interaction between DNA methylation of tripartite motif containing 27 (cg05293407 TRIM27 ) and smoking has previously been identified to reveal histologically heterogeneous effects of TRIM27 DNA methylation on early‐stage non‐small‐cell lung cancer (NSCLC) survival. However, to understand the complex mechanisms underlying NSCLC progression, we searched three‐way interactions. A two‐phase study was adopted to identify three‐way interactions in the form of pack‐year of smoking (number of cigarettes smoked per day × number of years smoked) × cg05293407 TRIM27 × epigenome‐wide DNA methylation CpG probe. Two CpG probes were identified with FDR‐q ≤ 0.05 in the discovery phase and P ≤ 0.05 in the validation phase: cg00060500 KIAA0226 and cg17479956 EXT2 . Compared to a prediction model with only clinical information, the model added 42 significant three‐way interactions using a looser criterion (discovery: FDR‐q ≤ 0.10, validation: P ≤ 0.05) had substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3‐year and 5‐year survival. Our research identified the complex interaction effects among multiple environment and epigenetic factors, and provided therapeutic target for NSCLC patients. We performed a two‐phase designed epigenome‐wide three‐way gene‐smoking interaction study of NSCLC survival and identified two CpG probes (cg00060500 KIAA0226 and cg17479956 EXT2 ), together with pack‐year of smoking and cg05293407 TRIM27 , exhibiting significant three‐way interaction effects. Meanwhile, these significant three‐way interactions substantially improved the area under the receiver operating characteristic curve (AUC) of the prognostic prediction model for both 3‐ and 5‐year survival.
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影响因子：
3.7
作者：
Marabita F;Almgren M;Lindholm ME;Ruhrmann S;Fagerström-Billai F;Jagodic M;Sundberg CJ;Ekström TJ;Teschendorff AE;Tegnér J;Gomez-Cabrero D
通讯作者：
Gomez-Cabrero D
影响因子：
6.6
作者：
Bjaanæs MM;Fleischer T;Halvorsen AR;Daunay A;Busato F;Solberg S;Jørgensen L;Kure E;Edvardsen H;Børresen-Dale AL;Brustugun OT;Tost J;Kristensen V;Helland Å
通讯作者：
Helland Å
跨组学生物标志物模型提高了早期肺腺癌的预后预测准确性。
影响因子：
5.2
作者：
Dong, Xuesi;Zhang, Ruyang;Christiani, David C.
通讯作者：
Christiani, David C.
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
影响因子：
5.2
作者：
Chen, Chao;Wei, Yongyue;Christiani, David C.
通讯作者：
Christiani, David C.
DOI：
10.1111/j.2517-6161.1995.tb02031.x
发表时间：
1995-01-01
影响因子：
5.8
作者：
BENJAMINI, Y;HOCHBERG, Y
通讯作者：
HOCHBERG, Y