Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease.
Epigenetic clustering of lung adenocarcinomas based on DNA methylation profiles in adjacent lung tissue: Its correlation with smoking history and chronic obstructive pulmonary disease.
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DOI：
10.1002/ijc.28684
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发表时间：
2014-07-15
影响因子：
6.4
通讯作者：
Kanai, Yae
中科院分区：
文献类型：
--
作者：
Sato, Takashi;Arai, Eri;Kohno, Takashi;Takahashi, Yoriko;Miyata, Sayaka;Tsuta, Koji;Watanabe, Shun-ichi;Soejima, Kenzo;Betsuyaku, Tomoko;Kanai, Yae
关键词：
本研究的目的是阐明DNA甲基化改变在肺癌发生过程中的意义。使用来自肺腺癌（LADC）患者学习队列的139对非癌性肺组织（N）和肿瘤组织（T）的配对样品进行Infinium测定。还分析了来自验证队列的50个配对N和T样本。相对于来自无原发性肺肿瘤患者的正常肺组织，在N样本中发生了1，928个探针上的DNA甲基化改变，并且在T样本中遗传或加强。在所有26，447个探针上使用N个样品中的DNA甲基化水平的无监督分层聚类将患者亚聚类为聚类I（n = 32）、聚类II（n = 35）和聚类III（n = 72）。簇I中的LADC从重度吸烟者的慢性阻塞性肺疾病（COPD）的炎症背景发展而来，并且具有局部侵袭性。聚类II中的大多数患者为非吸烟者，结局良好。在轻度吸烟者中发展的簇III中的LADC是最具侵袭性的（经常显示淋巴管和血管侵袭、淋巴结转移和晚期病理阶段），并且具有较差的结果。每个簇的标志基因的DNA甲基化水平，如IRX2，HOXD 8，SPARCL 1，RGS5和EI 24，再次与验证队列中的临床病理学特征相关。反映致癌因素如吸烟和COPD的DNA甲基化谱似乎在LADC患者的非癌性肺组织中建立，并且可能决定个体患者中肿瘤发展的侵袭性，从而决定患者的结局。
The aim of this study was to clarify the significance of DNA methylation alterations during lung carcinogenesis. Infinium assay was performed using 139 paired samples of non-cancerous lung tissue (N) and tumorous tissue (T) from a learning cohort of patients with lung adenocarcinomas (LADCs). Fifty paired N and T samples from a validation cohort were also analyzed. DNA methylation alterations on 1,928 probes occurred in N samples relative to normal lung tissue from patients without primary lung tumors, and were inherited by, or strengthened in, T samples. Unsupervised hierarchical clustering using DNA methylation levels in N samples on all 26,447 probes subclustered patients into Cluster I (n = 32), Cluster II (n = 35) and Cluster III (n = 72). LADCs in Cluster I developed from the inflammatory background in chronic obstructive pulmonary disease (COPD) in heavy smokers and were locally invasive. Most patients in Cluster II were non-smokers and had a favorable outcome. LADCs in Cluster III developed in light smokers were most aggressive (frequently showing lymphatic and blood vessel invasion, lymph node metastasis and an advanced pathological stage), and had a poor outcome. DNA methylation levels of hallmark genes for each cluster, such as IRX2, HOXD8, SPARCL1, RGS5 and EI24, were again correlated with clinicopathological characteristics in the validation cohort. DNA methylation profiles reflecting carcinogenetic factors such as smoking and COPD appear to be established in non-cancerous lung tissue from patients with LADCs and may determine the aggressiveness of tumors developing in individual patients, and thus patient outcome.
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影响因子：
3.8
作者：
Arai, Eri;Kanai, Yae
通讯作者：
Kanai, Yae
影响因子：
4.2
作者：
Kanai, Motoshi;Hamada, Jun-Ichi;Moriuchi, Tetsuya
通讯作者：
Moriuchi, Tetsuya
影响因子：
3
作者：
Hu, Lizhen;Sekine, Michikazu;Kagamimori, Sadanobu
通讯作者：
Kagamimori, Sadanobu
影响因子：
4.7
作者：
Peng, Dun-Fa;Kanai, Yae;Hirohashi, Setsuo
通讯作者：
Hirohashi, Setsuo
DOI：
10.1073/pnas.1203525109
发表时间：
2012-09-11
影响因子：
11.1
作者：
Hurley, Paula J.;Marchionni, Luigi;Schaeffer, Edward M.
通讯作者：
Schaeffer, Edward M.