Molecular Signature of Smoking in Human Lung Tissues
Molecular Signature of Smoking in Human Lung Tissues
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DOI：
10.1158/0008-5472.can-12-1160
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发表时间：
2012-08-01
期刊：
影响因子：
11.2
通讯作者：
Laviolette, Michel
中科院分区：
文献类型：
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作者：
Bosse, Yohan;Postma, Dirkje S.;Laviolette, Michel
吸烟是肺癌的主要危险因素。为了识别吸烟引起的基因失调，并区分戒烟后可逆和持续的基因表达变化，我们对853例肺癌患者的非肿瘤肺组织进行了全基因组基因表达谱分析。研究人员比较了从未吸烟者和目前吸烟者的基因表达水平，并研究了前吸烟者基因表达的时间依赖性变化。在发现组中，吸烟组之间共有3，223个转录本差异表达（n = 344，P < 1.29 x 10（-6））。大量的吸烟诱导的基因也验证了两个复制集（n = 285和224），和599个转录本的基因表达签名始终分离从来没有从目前的吸烟者在所有三个集。大多数这些基因的表达恢复到戒烟后从不吸烟者的水平，虽然正常化的时间过程在转录本之间有很大差异。此外，一些基因表现出非常缓慢或不可逆的表达，包括SERPIND 1，这被发现是最一致的基因永久改变吸烟在三组。因此，我们的研究结果表明，吸烟使许多基因失调，其中许多基因在戒烟后恢复正常。然而，即使在戒烟几十年后，一部分基因仍然改变，至少部分地解释了前吸烟者患肺癌的剩余风险。Cancer Res; 72（15）; 3753-63. (C)2012年AACR。
Cigarette smoking is the leading risk factor for lung cancer. To identify genes deregulated by smoking and to distinguish gene expression changes that are reversible and persistent following smoking cessation, we carried out genome-wide gene expression profiling on nontumor lung tissue from 853 patients with lung cancer. Gene expression levels were compared between never and current smokers, and time-dependent changes in gene expression were studied in former smokers. A total of 3,223 transcripts were differentially expressed between smoking groups in the discovery set (n = 344, P < 1.29 x 10(-6)). A substantial number of smoking-induced genes also were validated in two replication sets (n = 285 and 224), and a gene expression signature of 599 transcripts consistently segregated never from current smokers across all three sets. The expression of the majority of these genes reverted to never-smoker levels following smoking cessation, although the time course of normalization differed widely among transcripts. Moreover, some genes showed very slow or no reversibility in expression, including SERPIND1, which was found to be the most consistent gene permanently altered by smoking in the three sets. Our findings therefore indicate that smoking deregulates many genes, many of which reverse to normal following smoking cessation. However, a subset of genes remains altered even decades following smoking cessation and may account, at least in part, for the residual risk of lung cancer among former smokers. Cancer Res; 72(15); 3753-63. (C) 2012 AACR.