Smoking-Related Gene Expression in Laser Capture-Microdissected Human Lung.
Smoking-Related Gene Expression in Laser Capture-Microdissected Human Lung.
复制标题
激光捕获显微解剖人肺中与吸烟相关的基因表达。
DOI：
10.1158/1078-0432.ccr-09-1694
复制
发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Spivack,SimonD
中科院分区：
文献类型：
--
作者：
Tan,Xiang-Lin;Wang,Tao;Xiong,Shengli;Kumar,ShaliniV;Han,Weiguo;Spivack,SimonD
目的：定量表达的个体间差异可能是肺癌倾向的基础。为了在肺区室特异性基础上确定精确的个体基因表达特征，我们研究了编码细胞色素P450（P450）1B 1、2A 13、GST P1和肿瘤抑制基因ep 16的致癌物代谢基因在来自62名吸烟者和非吸烟者的人肺泡区室（AC）和支气管上皮区室（BEC）肺组织的激光捕获显微切割样本中的表达。烟草暴露通过血浆尼古丁、可替宁和吸烟史来确定。采用我们的RNA特异性qRT-PCR策略测定精确的mRNA表达，并与详细的人口统计学和临床特征相关。与血浆尼古丁水平呈正相关（P= 0.008）;与血浆可替宁水平呈正相关（P= 0.001）;（B）AC组GST 1（3）BEC中GSTP 1与血浆可替宁水平呈正相关（P= 0.003（与吸烟剂量呈负相关，P= 0.043;与职业危险度呈负相关，P= 0.019）; CYP 2A 13在AC中很少表达，在BEC中不表达; p16表达与任何测量因素均不相关。对于每一个基因，受试者表现出的表达是单独一致的这些隔间。在这个试点analysis.Conclusions：肺mRNA表达和烟草暴露之间的关联意味着，基因烟草相互作用是一个可测量的数量性状，虽然与广泛的个体间变异的mRNA表达与肺癌的风险没有明确的关联。在个体中，这些基因的肺泡和支气管室的基因表达往往是一致的，控制了近端烟草暴露。(Clin Cancer Res 2009;15（24）：7562-70）
Purpose:Interindividual differences in quantitative expression could underlie a propensity for lung cancer. To determine precise individual gene expression signatures on a lung compartment–specific basis, we investigated the expression of carcinogen metabolism genes encoding cytochromes P450 (CYP)1B1, 2A13, GSTP1, and a tumor suppressor genep16in laser capture–microdissected samples of human alveolar compartment (AC) and bronchial epithelial compartment (BEC) lung tissue from 62 smokers and nonsmokers.Experimental Design:Tobacco exposure was determined by plasma nicotine, cotinine, and smoking history. Precise mRNA expression was determined using our RNA-specific qRT-PCR strategy, and correlated with detailed demographic and clinical characteristics.Results:Several correlations of mRNA expression included (a)CYP1B1in AC (positively with plasma nicotine level,P= 0.008; plasma cotinine level,P= 0.001), (b)GSTP1in AC (positively with plasma cotinine level,P= 0.003), and (c)GSTP1in BEC (negatively with smoke dose,P= 0.043; occupational risk,P= 0.019).CYP2A13was rarely expressed in AC and not expressed in BEC.p16expression was not correlated with any measured factor. For each gene, subjects showed expression that was individually concordant between these compartments. No clear association of mRNA expression with lung cancer risk was observed in this pilot analysis.Conclusions:The association between lung mRNA expression and tobacco exposure implies that gene-tobacco interaction is a measurable quantitative trait, albeit with wide interindividual variation. Gene expression tends to be concordant for alveolar and bronchial compartments for these genes in an individual, controlling for proximate tobacco exposure. (Clin Cancer Res 2009;15(24):7562–70)