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Gene expression profiling of Barrett's esophagus, adenocarcinoma, esophageal squamous epithelium and squamous cell carcinoma

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Qing Wang

PROVIDER: E-GEOD-26886 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Gene expression profiling of Barrett's esophagus, adenocarcinoma, esophageal squamous epithelium and squamous cell carcinoma

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.

2013-10-18 | GSE26886 | GEO

Transformation of Barrett's esophagus stem cell, gastric cardia stem cells and normal esophagus stem cells

Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Transplantation of transformed Barrett’s stem cells yielded tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells produced squamous cell carcinomas. These findings define a stem cell target in a precancerous lesion for preemptive therapies.

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GLOBAL CHANGES IN GENE EXPRESSION OF BARRETT'S ESOPHAGUS COMPARED TO NORMAL SQUAMOUS ESOPHAGUS AND GASTRIC CARDIA TISSUES

Project description:Barrett’s esophagus (BE) is a metaplastic precursor lesion of esophageal adenocarcinoma (EA), the most rapidly increasing cancer in western societies. While the prevalence of BE is increasing, the vast majority of EA occurs in patients with undiagnosed BE. Thus, we sought to identify genes that are altered in BE compared to the normal mucosa of the esophagus, and which may be potential biomarkers for the development or diagnosis of BE. We performed gene expression analysis using HG-U133A Affymetrix chips on fresh frozen tissue samples of Barrett’s metaplasia and matched normal mucosa from squamous esophagus (NE) and gastric cardia (NC) in 43 BE patients.

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Paired non-cancerous and cancerous miRNA expression of esophageal adenocarcinoma and squamous cell carcinoma patients

Project description:Identifying biomarkers predictive for early esophageal cancer detection is critical considering the dismal survival rates. We investigated the involvement of microRNAs (miRNAs), their utility as biomarkers, and their association with survival in esophageal cancer, including Barrett’s associated and sporadic adenocarcinoma (ADC), and squamous cell carcinoma (SCC). MiRNA expression was measured in cancerous and adjacent non-cancerous tissue pairs collected from 76 US and Japanese patients enrolled in 3 distinct cohorts. In ADC patients, miR-21, miR-194, miR-293, and miR-223 expression was elevated, while miR-375 and miR-203 expression was reduced in cancerous tissue compared to non-cancerous tissue. Increased levels of miR-192 and miR-194 were observed in Barrett’s associated compared to sporadic ADC cancerous tissue. In SCC patients, miR-21, miR-181b, miR-155, and miR-146b expression was elevated while miR-375 and miR-203 levels were reduced in cancerous tissue compared to non-cancerous tissue. Significantly, elevated mir-21 expression in non-cancerous tissue was strongly associated with worse prognosis, independent of nodal status and age. Sample classification using miRNA expression yielded accuracies as high as 86% for diagnosis and 78% for Barrett’s esophagus status. Our results highlight that miRNAs are deregulated in esophageal carcinogenesis and Barrett’s esophagus, and that their expression is associated with survival in cancer patients. Sample classification using miRNA expression demonstrates their potential utility as biomarkers for esophageal carcinoma diagnosis. MiRNA microarray expression was measured using miRNA microarray chips version 3 (Ohio State University) in 44 SCC cases and 32 ADC cases, of which 18 were also diagnosed with Barrett’s esophagus.

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Project description:Barrett’s esophagus confers significant risk of esophageal adenocarcinoma. We have established the cloning of patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Barrett's esophagus stem cells (BE), gastric cardia stem cells (GC) and normal esophagus stem cells (Eso) from 12 patients were cloned (For BE: 12 patients, GC: 12 patients and Eso: 2 patients). Keratin 5 positive and Keratin 7 positive cells were cloned from human fetal esophageal epithelium. Using air liquid interface culture system, stem cells were induced to differentiate into mature epithelial structures.

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2021-04-24 | GSE173169 | GEO

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Cloning Barrett’s esophagus stem cells

Project description:Barrett’s esophagus is a precancerous lesion that confers a significant risk of esophageal adenocarcinoma. Strategies for selective eradication of Barrett’s have been stymied by our inability to identify the Barrett’s stem cell. Here we employ novel technologies to clone patient-matched stem cells of Barrett’s, gastric, and esophageal epithelium. Genomic analyses of Barrett’s stem cells reveal a patient-specific mutational spectrum ranging from low somatic variation similar to patient-matched gastric epithelial stem cells to ones marked by extensive heterozygous alteration of genes implicated in tumor suppression, epithelial planarity, and epigenetic regulation. Transplantation of transformed Barrett’s stem cells yields tumors with hallmarks of esophageal adenocarcinoma, whereas transformed esophageal stem cells yield squamous cell carcinomas. Thus Barrett’s develops from cells distinct from local eponymous epithelia, emerges without obvious driver mutations, and likely progresses through and from the generation of dominant clones. These findings define a stem cell target for preemptive therapies of a precancerous lesion.

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