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Down‐regulation of the claudin‐18 gene, identified through serial analysis of gene expression data analysis, in gastric cancer with an intestinal phenotype
Author(s) -
Sanada Y,
Oue N,
Mitani Y,
Yoshida K,
Nakayama H,
Yasui W
Publication year - 2006
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1922
Subject(s) - claudin , immunostaining , biology , carcinogenesis , phenotype , cancer , serial analysis of gene expression , gene expression , cancer research , stomach , microbiology and biotechnology , gene , reverse transcription polymerase chain reaction , real time polymerase chain reaction , gene expression profiling , pathology , immunohistochemistry , tight junction , medicine , immunology , genetics , biochemistry
Abstract Gastric cancer (GC) is one of the most common malignancies worldwide. Genes whose expression is down‐regulated in GC may be tumour suppressor genes. In the present study, genes with decreased expression in GC were screened for by serial analysis of gene expression (SAGE) data analysis and reverse transcription (RT)‐polymerase chain reaction (PCR), and CLDN18 (encoding claudin‐18) was identified. Quantitative RT‐PCR revealed that expression of CLDN18 was down‐regulated in 13 (56.5%) of 23 GCs. Immunostaining showed that normal gastric mucosa and Paneth cells of the duodenum expressed claudin‐18 on cell membranes. Expression of claudin‐18 was reduced in several intestinal metaplasias of the stomach. Of 20 samples of gastric adenoma, 18 (90.0%) showed decreased claudin‐18 expression. Down‐regulation of claudin‐18 was observed in 84 of 146 GCs (57.5%) and correlated with poor survival in 65 advanced GCs ( p = 0.0346). In addition, expression of the gastric and intestinal phenotypes of GC was examined by immunostaining for MUC5AC, MUC6, MUC2, and CD10. Of 38 GCs showing only the intestinal phenotype, down‐regulation of claudin‐18 was observed in 28 (73.7%), whereas in the remaining 108 GC cases, down‐regulation of claudin‐18 was observed in 56 (51.9%) ( p = 0.0224). These results indicate that claudin‐18 is a good marker of poor survival in GC. Down‐regulation of claudin‐18 may be involved in GCs with an intestinal phenotype, and may be an early event in gastric carcinogenesis. Copyright © 2006 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.