Project description:The aim of this study is to generate and validate biomarkers to stratify patients with Barrett’s esophagus in terms of risk for developing cancer. We studied gene expression profiling in 69 frozen specimens, consisting of esophageal squamous epithelium from 19 healthy subjects, 20 specimens from patients with Barrett’s esophagus and 21 cases of esophageal adenocarcinoma, 9 cased of esophageal squamous cell carcinoma by whole genome microarray analysis. Laser capture microdissection technique was applied to procure cells from defined regions of Barrett’s esophagus metaplasia and esophageal adenocarcinoma. Microarray results were validated by quantitative real-time polymerase chain reaction (qRT-PCR) in an independent cohort consisting of 42 cases. Furthermore, immunohistochemistry was performed using antibodies to two selected target molecules on a third independent cohort of 36 specimens, consisting of 36 cases. A total of 1176 genes were associated significantly with esophageal adenocarcinoma. The expression pattern of a 4 gene signature with the highest discriminant score based on linear discriminant analysis (GeneSpring GX10.2), was identified and validated by qRT-PCR in independent cohort. Gene expression profiling of 20 specimens of Barrett's esophagus patients, 21 specimens of adenocarcinoma patients and 19 biopsies from patients with normal esophageal squamous epithelium, 9 specimens of squamous cell carcinoma were studied.
Project description:Barrett's esophagus is a metaplastic condition of the distal esophagus, characterized by the replacement of normal squamous epithelium by columnar epithelium. Patients with BE have an increased risk of developing esophageal adenocarcinoma. MicroRNAs have been implicated to be disease and tissue specific, however limited data of microRNA expression in the esophagus is available. Therefore we evaluated microRNA expression profiles of esophageal adenocarcinoma and compared these with Barrett's esophagus and normal squamous esophagus.
Project description:SAGE libraries made of squamous esophagus tissue, primary cell culture or esophageal squamous cell carcinoma Keywords: SAGE analysis of different tissues squamous esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. primary cell culture was from 1 male Barrett's esophagus patient. Esophageal squamous cell carcinoma was from a patient known to have ESCC
Project description:To test the hypothesis that there is a specific miRNA expression signature which characterizes Barrett's esophagus development and progression, we performed miRNA microarray analysis comparing normal esophageal squamous epithelium with all the phenotypic lesions seen in the Barrett's carcinogenic process miRNA microarray analysis was performed in a series of 14 normal esophageal squamous epithelium samples, 14 Barrett's mucosa samples, 7 low-grade intra-epithelial neoplasia samples, 5 high-grade intra-epithelial neoplasia samples and 11 Barrett's adenocarcinoma samples
Project description:Barrett's esophagus transcriptome was analysed and compared with Barrett's esophagus primary cell culture and esophageal adenocarcinoma. Keywords: SAGE analysis to compare tissues Barrett's esophagus biopsy was taken from 1 male metaplastic Barrett's esophagus patient. Barrett's esophagus primary cell culture was cultures from a biopsy taken from a Barrett's esophagus patient and cultured for about 4 to 5 weeks. Esophageal adenocarcinoma was taken from a patient known to have cancer and previously Barrett's esophagus
Project description:miR-223 is step-wise increasingly up-regulated in the normal esophagus - Barrett's esophagus -esophageal adenocarcinoma carcinoma sequence. In this study, we aimed to determine the function of miR-223 in esophageal adenocarcinoma carcinogenesis.
Project description:RNA-seq was performed on esophageal adenocarcinoma (EAC), Barrett's without dysplasia, Barrett's with low-grade dysplasia (LGD) and normal squamous esophagus tissue to find early alterations in the transcriptome level turning Barrett's dysplastic.
Project description:Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett’s esophagus have not been resolved in humans. Here, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly revealed that the squamous esophagus and gastric cardia contained cells belonging to common lineages that also included transitional basal progenitor cells; both esophageal and gastric tissues were also related to Barrett's esophagus. Barrett’s esophagus biopsies consisted of multiple clones, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic lesions were initiated by the expansion of a single molecularly aberrant Barrett’s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the disease trajectory, from its origin to cancer.
Project description:Barrett's esophagus is a common type of metaplasia and a precursor of esophageal adenocarcinoma. However, the cell states and lineage connections underlying the origin, maintenance, and progression of Barrett’s esophagus have not been resolved in humans. Here, we performed single-cell lineage tracing and transcriptional profiling of patient cells isolated from metaplastic and healthy tissue. Our analysis unexpectedly revealed that the squamous esophagus and gastric cardia contained cells belonging to common lineages that also included transitional basal progenitor cells; both esophageal and gastric tissues were also related to Barrett's esophagus. Barrett’s esophagus biopsies consisted of multiple clones, with lineages that contained all progenitor and differentiated cell types. In contrast, precancerous dysplastic lesions were initiated by the expansion of a single molecularly aberrant Barrett’s esophagus clone. Together, these findings provide a comprehensive view of the cell dynamics of Barrett's esophagus, linking cell states along the disease trajectory, from its origin to cancer.
Project description:To test the hypothesis that there is a specific miRNA expression signature which characterizes Barrett's esophagus development and progression, we performed miRNA microarray analysis comparing normal esophageal squamous epithelium with the two different metaplastic lesions occuring within Barrett's mucosa (i.e. gastric metaplasia and intestinal metaplasia). Samples of H. pylori-related gastritis and gastric intestinal metaplasia were also considered in the definition of esophageal-specific miRNAs. miRNA microarray analysis was performed in a series of samples obtained from (a) 10 histologically-proven long-segment Barrett's esophagus patients; (b) 10 patients with H. pylori-related chronic atrophic gastritis. Overall, 10 normal esophageal squamous epithelium samples, 10 esophageal intestinal metaplasia samples, 10 esophageal gastric metaplasia samples, 10 H. pylori -related gastritis samples (no atrophic lesion detected; obtained from the antrum) and 10 gastric intestinal metaplasia samples (obtained from the antrum) were considered.