Open AccessClinicopathologic and molecular characteristics of gastric cancer showing gastric and intestinal mucin phenotype
Author(s) -
Oue Naohide,
Sentani Kazuhiro,
Sakamoto Naoya,
Yasui Wataru
Publication year - 2015
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12706
Subject(s) - phenotype , ectopic expression , biology , cdx2 , mucin 2 , cancer , cancer research , mutation , claudin , gene , genetics , gene expression , tight junction , homeobox
Gastric cancer ( GC ), one of the most common human cancers, can be classified into gastric or intestinal phenotype according to mucin expression. TP 53 mutation, allelic deletion of the APC gene and nuclear staining of β‐catenin are frequently detected in the intestinal phenotype of GC , whereas CDH 1 gene mutation, microsatellite instability and DNA hypermethylation of MLH 1 are common events in the gastric phenotype of GC . Our Serial Analysis of Gene Expression ( SAGE ) and Escherichia coli ampicillin secretion trap ( CAST ) analyses revealed that CDH 17 , REG 4 , OLFM 4 , HOXA 10 , DSC 2 , TSPAN 8 and TM 9 SF 3 are upregulated in GC and that CLDN 18 is downregulated in GC . Expression of CDH 17 , REG 4 , HOXA 10 and DSC 2 and downregulation of CLDN 18 are observed in the intestinal phenotype of GC . In contrast, OLFM 4 is expressed in the gastric phenotype of GC . Expression of TSPAN 8 , TM 9 SF 3 and HER 2 are not associated with either gastric or intestinal phenotypes. Ectopic CDX 2 expression plays a key function in the GC intestinal phenotype. MUC 2 , CDH 17 , REG 4 , DSC 2 and ABCB 1 are direct targets of CDX 2. Importantly, these genes encode transmembrane/secretory proteins, indicating that the microenvironment as well as cancer cells are also different between gastric and intestinal phenotypes of GC .