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Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival

BACKGROUND: The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastr...

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Autores principales: Eftang, Lars L, Esbensen, Ying, Tannæs, Tone M, Blom, Gustav P, Bukholm, Ida RK, Bukholm, Geir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029627/
https://www.ncbi.nlm.nih.gov/pubmed/24321518
http://dx.doi.org/10.1186/1471-2407-13-586
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author Eftang, Lars L
Esbensen, Ying
Tannæs, Tone M
Blom, Gustav P
Bukholm, Ida RK
Bukholm, Geir
author_facet Eftang, Lars L
Esbensen, Ying
Tannæs, Tone M
Blom, Gustav P
Bukholm, Ida RK
Bukholm, Geir
author_sort Eftang, Lars L
collection PubMed
description BACKGROUND: The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. METHODS: Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. RESULTS: 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CONCLUSIONS: CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic value. IL-8 and CLDN1 may represent central links between the gene response seen in acute H. pylori infection of gastric epithelial cells, and ultimately gastric cancer.
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spelling pubmed-40296272014-05-22 Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival Eftang, Lars L Esbensen, Ying Tannæs, Tone M Blom, Gustav P Bukholm, Ida RK Bukholm, Geir BMC Cancer Research Article BACKGROUND: The genetic changes in gastric adenocarcinoma are extremely complex and reliable tumor markers have not yet been identified. There are also remarkable geographical differences in the distribution of this disease. Our aim was to identify the most differentially regulated genes in 20 gastric adenocarcinomas from a Norwegian selection, compared to matched normal mucosa, and we have related our findings to prognosis, survival and chronic Helicobacter pylori infection. METHODS: Biopsies from gastric adenocarcinomas and adjacent normal gastric mucosa were obtained from 20 patients immediately following surgical resection of the tumor. Whole genome, cDNA microarray analysis was performed on the RNA isolated from the sample pairs to compare the gene expression profiles between the tumor against matched mucosa. The samples were microscopically examined to classify gastritis. The presence of H. pylori was examined using microscopy and immunohistochemistry. RESULTS: 130 genes showed differential regulation above a predefined cut-off level. Interleukin-8 (IL-8) and Claudin-1 (CLDN1) were the most consistently up-regulated genes in the tumors. Very high CLDN1 expression in the tumor was identified as an independent and significant predictor gene of reduced post-operative survival. There were distinctly different expression profiles between the tumor group and the control mucosa group, and the histological subsets of mixed type, diffuse type and intestinal type cancer demonstrated further sub-clustering. Up-regulated genes were mapped to cell-adhesion, collagen-related processes and angiogenesis, whereas normal intestinal functions such as digestion and excretion were associated with down-regulated genes. We relate the current findings to our previous study on the gene response of gastric epithelial cells to H. pylori infection. CONCLUSIONS: CLDN1 was highly up-regulated in gastric cancer, and CLDN1 expression was independently associated with a poor post-operative prognosis, and may have important prognostic value. IL-8 and CLDN1 may represent central links between the gene response seen in acute H. pylori infection of gastric epithelial cells, and ultimately gastric cancer. BioMed Central 2013-12-10 /pmc/articles/PMC4029627/ /pubmed/24321518 http://dx.doi.org/10.1186/1471-2407-13-586 Text en Copyright © 2013 Eftang et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Eftang, Lars L
Esbensen, Ying
Tannæs, Tone M
Blom, Gustav P
Bukholm, Ida RK
Bukholm, Geir
Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title_full Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title_fullStr Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title_full_unstemmed Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title_short Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival
title_sort up-regulation of cldn1 in gastric cancer is correlated with reduced survival
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4029627/
https://www.ncbi.nlm.nih.gov/pubmed/24321518
http://dx.doi.org/10.1186/1471-2407-13-586
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