Wang S, Zhan M, Yin J, Abraham J M, Mori Y, Sato F, Xu Y, Olaru A, Berki A T, Li H, Schulmann K, Kan T, Hamilton J P, Paun B, Yu M M, Jin Z, Cheng Y, Ito T, Mantzur C, Greenwald B D, Meltzer S J
Division of Gastroenterology, Department of Medicine, University of Maryland School of Medicine, Baltimore, USA.
Oncogene. 2006 Jun 1;25(23):3346-56. doi: 10.1038/sj.onc.1209357. Epub 2006 Jan 30.
To investigate the relationship between Barrett's esophagus (BE) and esophageal adenocarcinoma (EAC), we determined gene expression profiles of discrete pathological stages of esophageal neoplasia using a sequence-verified human cDNA microarray. Fifty one RNAs, comprising 24 normal esophagi (NE), 18 BEs, and nine EACs were hybridized to cDNA microarrays. Five statistical analyses were used for the data analysis. Genes showing significantly different expression levels among the three sample groups were identified. Genes were grouped into functional categories based on the Gene Ontology Consortium. Surprisingly, the expression pattern of BE was significantly more similar to EAC than to NE, notwithstanding the known histopathologic differences between BE and EAC. The pattern of NE was clearly distinct from that of EAC. Thirty-six genes were the most differentially modulated, according to these microarray data, in BE-associated neoplastic progression. Twelve genes were significantly differentially expressed in cancer-associated BE's plus EAC (as a single combined tissue group) vs noncancer-associated BE's. These genes represent potential biomarkers to diagnose EAC at its early stages. Our results demonstrate that molecular events at the transcriptional level in BE are remarkably similar to BE's-associated adenocarcinoma of the esophagus. This finding alarmingly implies that BE is biologically closer to cancer than to normal esophagus, and that the cancer risk of BE is perhaps higher than we had imagined. These findings suggest that changes modulated at the molecular biologic level supervene earlier than histologic changes, and that BE is an early intermediate stage in the process of EAC.
为研究巴雷特食管（BE）与食管腺癌（EAC）之间的关系，我们使用经序列验证的人类cDNA微阵列，确定了食管肿瘤不同病理阶段的基因表达谱。将包含24个正常食管（NE）、18个BE和9个EAC的51个RNA与cDNA微阵列进行杂交。数据分析采用了五种统计分析方法。确定了在三个样本组中表达水平有显著差异的基因。根据基因本体联盟将基因分为功能类别。令人惊讶的是，尽管已知BE和EAC在组织病理学上存在差异，但BE的表达模式与EAC比与NE更相似。NE的模式与EAC明显不同。根据这些微阵列数据，在BE相关的肿瘤进展中，有36个基因的调控差异最大。在癌症相关的BE加EAC（作为一个单一的联合组织组）与非癌症相关的BE中，有12个基因有显著差异表达。这些基因代表了在EAC早期诊断的潜在生物标志物。我们的结果表明，BE转录水平的分子事件与BE相关的食管腺癌非常相似。这一发现令人担忧地暗示，BE在生物学上更接近癌症而非正常食管，并且BE的癌症风险可能比我们想象的更高。这些发现表明，分子生物学水平上的调控变化比组织学变化更早出现，并且BE是EAC过程中的早期中间阶段。
