Altered expression of TFF-1 and CES-2 in Barrett's esophagus and associated adenocarcinomas
Altered expression of TFF-1 and CES-2 in Barrett's esophagus and associated adenocarcinomas
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DOI：
10.1593/neo.04715
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发表时间：
2005-04-01
期刊：
影响因子：
4.8
通讯作者：
Powell, SM
中科院分区：
文献类型：
--
作者：
Fox, CA;Sapinoso, LM;Powell, SM
寻找生物标记物来识别Barrett‘s食道(BE)易发生恶性病变的个体是目前一个紧迫的问题。我们利用基因表达谱来比较正常食道和胃、BE和腺癌(AC)的分子特征，以确定这些潜在的生物标志物。通过38个独特的RNA上的寡核苷酸微阵列分析了超过22,000个基因。对2849个基因的子集进行了无监督和有监督的聚类，这些基因在样本中差异最大。非监督聚类发现了两个可识别的分子BE谱，其中一个是相似的正常胃组织(“BE1”)，另一个是几个AC标本共有的(“BE2”)。BE1谱包括几个被描述为肿瘤抑制基因的基因的表达，最著名的是三叶因子1(TFF-1)。BE2谱包括以前在癌症中发现的过度表达的基因，如羧酸酯酶-2(CES-2)。在BE向AC发展的晚期，IHC证实了TFF-1的缺失。它还揭示了CES-2在AC中上调，有文件证明在BE的存在下出现了CES-2。这些潜在的生物标志物，以及BE1和BE2基因的相对表达，可能会在未来得到验证，以帮助BE和相关AC患者的风险分层和指导治疗方案。
Identification of biomarkers to recognize individuals with Barrett's esophagus (BE) predisposed to develop malignancy is currently a pressing issue. We utilized gene expression profiling to compare molecular signatures of normal esophagus and stomach, BE, and adenocarcinoma (AC) to identify such potential biomarkers. Over 22,000 genes were analyzed by oligonucleotide microarrays on 38 unique RNA. Unsupervised and supervised clusterings were performed on a subset of 2849 genes that varied most significantly across the specimens. Unsupervised clustering identified two discernable molecular BE profiles, one of which was similar 0 normal gastric tissue ("BE1"), and another that was shared by several of the AC specimens ("BE2"). The BE1 profile included expression of several genes that have been described as tumor-suppressor genes, most notably trefoil factor 1 (TFF-1). The BE2 profile included expression of genes previously found overexpressed in cancers, such as carboxylesterase-2 (CES-2). IHC demonstrated the loss of TFF-1 late in the progression of BE to AC. It also revealed CES-2 as being upregulated in AC documented to have arisen in the presence of BE. These potential biomarkers, as well as the relative expression of genes from BE1 versus those from BE2, may be validated in the future to aid in risk stratification and guide treatment protocols in patients with BE and associated AC.