Alteration of protein expression and spliceosome pathway activity during Barrett's carcinogenesis

Autor: Angela Bureo Gonzalez, Coşkun Güzel, Michail Doukas, Christoph Stingl, Gerben E. Breimer, Sybren L. Meijer, Jacques J.G.H.M. Bergman, Kai Yi N. Phoa, Theo M. Luider
Přispěvatelé: Pathology, Gastroenterology and Hepatology, CCA - Imaging and biomarkers, Amsterdam Gastroenterology Endocrinology Metabolism, Neurology
Rok vydání: 2020
Předmět:
Zdroj: Journal of Gastroenterology
Journal of gastroenterology, 56(9), 791-807. Springer Japan
Journal of Gastroenterology, 56(9), 791-807. Springer Japan
ISSN: 1435-5922
0944-1174
Popis: Background Barrett’s esophagus (BE) is a known precursor lesion and the strongest risk factor for esophageal adenocarcinoma (EAC), a common and lethal type of cancer. Prediction of risk, the basis for efficient intervention, is commonly solely based on histologic examination. This approach is challenged by problems such as inter-observer variability in the face of the high heterogeneity of dysplastic tissue. Molecular markers might offer an additional way to understand the carcinogenesis and improve the diagnosis—and eventually treatment. In this study, we probed significant proteomic changes during dysplastic progression from BE into EAC. Methods During endoscopic mucosa resection, epithelial and stromal tissue samples were collected by laser capture microdissection from 10 patients with normal BE and 13 patients with high-grade dysplastic/EAC. Samples were analyzed by mass spectrometry-based proteomic analysis. Expressed proteins were determined by label-free quantitation, and gene set enrichment was used to find differentially expressed pathways. The results were validated by immunohistochemistry for two selected key proteins (MSH6 and XPO5). Results Comparing dysplastic/EAC to non-dysplastic BE, we found in equal volumes of epithelial tissue an overall up-regulation in terms of protein abundance and diversity, and determined a set of 226 differentially expressed proteins. Significantly higher expressions of MSH6 and XPO5 were validated orthogonally and confirmed by immunohistochemistry. Conclusions Our results demonstrate that disease-related proteomic alterations can be determined by analyzing minute amounts of cell-type-specific collected tissue. Further analysis indicated that alterations of certain pathways associated with carcinogenesis, such as micro-RNA trafficking, DNA damage repair, and spliceosome activity, exist in dysplastic/EAC.
Databáze: OpenAIRE
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