Transcriptional profiling suggests that Barrett's metaplasia is an early intermediate stage in esophageal adenocarcinogenesis

Abstract

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.

Gene expression profiling of esophageal cancer: Comparative analysis of Barrett's esophagus, adenocarcinoma, and squamous cell carcinoma

“…As with the previous study by Wang et al, 17 BE was found to cluster more closely with ADC than normal esophagus, a result consistent with the columnar phenotype of BE and ADC compared with the squamous phenotype of esophageal epithelium. Similarly, SCC clustered more closely with normal tissue then either BE or ADC.…”

“…These results are consistent with previous ontology analysis of ADC and BE. 17 Our analysis clearly shows the overlap in genes expressed in both BE and ADC and between ADC and SCC. However, we were also able to show the distinct nature of SCC and ADC.…”

“…Similar ontologies have previously been identified for genes differentially expressed in BE and ADC. 17 A number of categories were found over represented in the SCC and ADC samples. These included immune and inflammatory response genes, as well as collagen binding, peptidase activity, and extracellular matrix genes.…”

“…Previous analysis of esophageal samples through gene expression profiling have focused on specific histological subtypes. [12][13][14][15][16][17] Few studies to date have conducted comparative analysis of gene expression profiles of BE, ADC, and SCC tissue samples in the same study. Thus, to obtain insight into the molecular processes underlying tumorigenesis in the esophagus, we have a used a cDNA microarray approach to compare gene expression profiles of a large number of BE, ADC, and SCC with normal esophageal mucosa.…”

Roles of Fibroblast Growth Factor-inducible 14 in Hepatocellular Carcinoma

“…In addition, the role of Fn14 in glioma cell motility was associated with the activation of Rac1 and NF-κB signaling pathway (Tran et al, 2003;Tran et al, 2006). Fn14 was one of 12 disease progression correlating genes, with highest expression levels in esophageal 1 adenocarcinoma (Wang et al, 2006) and positive correlated with breast tumor metastasis, positive lymph node status and HER2-positive/ER-negative breast tumors (Willis et al, 2008). Generally, there is increasing evidence that Fn14 expression is elevated in a variety of human tumors, such as breast cancer, malignant glioma, esophageal adenocarcinoma, and pancreatic cancer (Han et al, 2002;Tran et al, 2006;Watts et al, 2007;Willis et al, 2008).…”