title: Up-regulation of CLDN1 in gastric cancer is correlated with reduced survival.
abstract: 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.
authors: Department of Clinical Molecular Biology and Laboratory Sciences (EpiGen), Division of Medicine, Akershus University Hospital and University of Oslo, N-1478 Nordbyhagen, Oslo, Norway. lars.eftang@medisin.uio.no.
authors: Lars L
authors: LL
authors: Eftang
authors: Ying
authors: Y
authors: Esbensen
authors: Tone M
authors: TM
authors: Tannæs
authors: Gustav P
authors: GP
authors: Blom
authors: Ida R K
authors: IR
authors: Bukholm
authors: Geir
authors: G
authors: Bukholm
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality / Q000601:surgery; D000368:Aged; D000369:Aged, 80 and over; D062445:Claudin-1 / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005743:Gastrectomy; D005753:Gastric Mucosa / Q000382:microbiology; D063990:Gene Ontology; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D011379:Prognosis; D016016:Proportional Hazards Models; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000382:microbiology / Q000401:mortality / Q000601:surgery; D059467:Transcriptome; D015854:Up-Regulation
chemical_list: C568108:CLDN1 protein, human; D062445:Claudin-1