Effect of active smoking on the human bronchial epithelium transcriptome.
Effect of active smoking on the human bronchial epithelium transcriptome.
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DOI：
10.1186/1471-2164-8-297
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发表时间：
2007-08-29
期刊：
影响因子：
4.4
通讯作者：
Lam S
中科院分区：
文献类型：
--
作者：
Chari R;Lonergan KM;Ng RT;MacAulay C;Lam WL;Lam S
肺癌是癌症相关死亡的最常见原因。烟草烟雾暴露是与肺癌相关的最强病因因素。在这项研究中，使用基因表达系列分析（SAGE），我们通过比较从当前，以前和从不吸烟者获得的临床标本的转录组，全面研究了主动吸烟的影响，并确定了戒烟后显示可逆和不可逆表达变化的基因。生成并分析了8名当前吸烟者、12名前吸烟者和4名从不吸烟者的支气管上皮的24个SAGE图谱。总共产生了3，111，471个SAGE标签，代表了超过11万个潜在的独特转录本，构成了迄今为止最大的人类SAGE研究。我们确定了1，733个组成型表达基因在当前，以前和从未吸烟者转录组。我们还确定了戒烟后可逆和不可逆的基因表达变化;可逆变化通常与异生物质代谢、核苷酸代谢或粘液分泌有关。发现TFF 3、CABYR和ENTPD 8的表达增加在戒烟后是可逆的。调节COX 2表达的GSK 3B的表达不可逆地降低。MUC 5AC表达仅部分逆转。使用定量RT-PCR对9名当前吸烟者、7名前吸烟者和6名从不吸烟者的次级队列进行选择基因的验证。一些与吸烟相关的基因的表达水平在戒烟后恢复到与从不吸烟者相似的水平，而另一些基因的表达似乎在长期戒烟后发生了永久性改变。这些不可逆转的变化可能是戒烟后肺癌风险持续存在的原因。
Lung cancer is the most common cause of cancer-related deaths. Tobacco smoke exposure is the strongest aetiological factor associated with lung cancer. In this study, using serial analysis of gene expression (SAGE), we comprehensively examined the effect of active smoking by comparing the transcriptomes of clinical specimens obtained from current, former and never smokers, and identified genes showing both reversible and irreversible expression changes upon smoking cessation. Twenty-four SAGE profiles of the bronchial epithelium of eight current, twelve former and four never smokers were generated and analyzed. In total, 3,111,471 SAGE tags representing over 110 thousand potentially unique transcripts were generated, comprising the largest human SAGE study to date. We identified 1,733 constitutively expressed genes in current, former and never smoker transcriptomes. We have also identified both reversible and irreversible gene expression changes upon cessation of smoking; reversible changes were frequently associated with either xenobiotic metabolism, nucleotide metabolism or mucus secretion. Increased expression of TFF3, CABYR, and ENTPD8 were found to be reversible upon smoking cessation. Expression of GSK3B, which regulates COX2 expression, was irreversibly decreased. MUC5AC expression was only partially reversed. Validation of select genes was performed using quantitative RT-PCR on a secondary cohort of nine current smokers, seven former smokers and six never smokers. Expression levels of some of the genes related to tobacco smoking return to levels similar to never smokers upon cessation of smoking, while expression of others appears to be permanently altered despite prolonged smoking cessation. These irreversible changes may account for the persistent lung cancer risk despite smoking cessation.
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影响因子：
3
作者：
Hovenberg, HW;Davies, JR;Carlstedt, I
通讯作者：
Carlstedt, I
DOI：
10.1097/00042737-200206000-00005
发表时间：
2002-06-01
影响因子：
2.1
作者：
Eliakim, R;Fan, QX;Babyatsky, MW
通讯作者：
Babyatsky, MW
影响因子：
10.3
作者：
Barsky, SH;Roth, MD;Tashkin, DP
通讯作者：
Tashkin, DP
影响因子：
10.3
作者：
HALPERN, MT;GILLESPIE, BW;WARNER, KE
通讯作者：
WARNER, KE
影响因子：
10
作者：
O'Donnell, RA;Richter, A;Wilson, SJ
通讯作者：
Wilson, SJ