Progression of Barrett's metaplasia to adenocarcinoma is associated with the suppression of the transcriptional programs of epidermal differentiation
Progression of Barrett's metaplasia to adenocarcinoma is associated with the suppression of the transcriptional programs of epidermal differentiation
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DOI：
10.1158/0008-5472.can-04-2490
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发表时间：
2005-04-15
期刊：
影响因子：
11.2
通讯作者：
Khodarev, NN
中科院分区：
文献类型：
--
作者：
Kimchi, ET;Posner, MC;Khodarev, NN
我们对24对正常食道上皮、巴雷特化生和食管腺癌样本进行了表达谱分析。代表三种不同组织学类型的匹配组织样本取自每个接受食管腺癌切除手术的患者。我们的分析比较了伴随正常鳞状上皮转化的分子变化与Barrett在个体患者中的食道癌和腺癌的分子变化，而不是在随机队列中。我们测试了一种假设，即表达谱可能揭示可用作从正常食道上皮到Barrett‘s食道和腺癌进展的分子标志物的基因集。使用U133A基因芯片(Affymetrix，Santa Clara，CA)进行表达谱分析，它代表了大约三分之二的人类基因组。最终选择的214个基因允许使用所选基因的二维分层聚类来区分正常食管鳞状上皮、Barrett‘s食管和腺癌的差异基因表达。这些数据表明Barrett‘s食管腺癌的发生与表皮分化相关基因的抑制有关，这些基因包括与表皮分化复合体相对应的基因1q21。对Barrett‘s食管腺癌中一致表达的基因进行相关性分析，发现21个基因代表疾病进展的潜在遗传标志和治疗干预的药物靶点。对基于DNA阵列实验选择的基因进行的聚合酶链式反应分析表明，对GATA6和SPRR3的比率的估计可以区分正常食道上皮、巴雷特异型增生和腺癌。
We did expressional profiling on 24 paired samples of normal esophageal epithelium, Barrett's metaplasia, and esophageal adenocarcinomas. Matching tissue samples representing the three different histologic types were obtained from each patient undergoing esophagectomy for adenocarcinoma. Our analysis compared the molecular changes accompanying the transformation of normal squamous epithelium with Barrett Is esophagus and adenocarcinoma in individual patients rather than in a random cohort. We tested the hypothesis that expressional profiling may reveal gene sets that can be used as molecular markers of progression from normal esophageal epithelium to Barrett's esophagus and adenocarcinoma. Expressional profiling was done using U133A GeneChip (Affymetrix, Santa Clara, CA), which represents approximately two thirds of the human genome. The final selection of 214 genes permitted the discrimination of differential gene expression of normal esophageal squamous epithelium, Barrett's esophagus, and adenocarcinoma using two-dimensional hierarchical clustering of selected genes. These data indicate that transformation of Barrett's esophagus to adenocarcinoma is associated with suppression of the genes involved in epidermal differentiation, including genes 1q21 loci and corresponding to the epidermal differentiation complex. Correlation analysis of genes concordantly expressed in Barrett's esophagus and adenocarcinoma revealed 21 genes that represent potential genetic markers of disease progression and pharmacologic targets for treatment intervention. PCR analysis of genes selected based on DNA array experiments revealed that estimation of the ratios of GATA6 to SPRR3 allows discrimination among normal esophageal epithelium, Barrett's dysplasia, and adenocarcinoma.