Characteristic gene expression profiles in the progression from normal gastric epithelial cells to moderate gastric epithelial dysplasia and to gastric cancer.
BACKGROUND
Gastric cancer ranks high among the most common causes of cancer-related death worldwide. This study was designed to explore key genes involved in the progression of normal gastric epithelial cells to moderate gastric epithelial dysplasia (mGED) and to gastric cancer.


METHODS
Twelve pairs of mGED tissues, gastric cancer tissues, and normal gastric tissues were collected by gastroscopy. Total RNA was then extracted and purified. After the addition of fluorescent tags, hybridization was carried out on a Gene chip microarray slide. Significance analysis of microarrays was performed to determine significant differences in gene expression between the different tissue types.


RESULTS
Microarray data analysis revealed totally 34 genes that were expressed differently: 18 highly expressed (fold change > 2; P < 0.01) and 16 down-regulated (fold change > 2; P < 0.01). Of the 34 genes, 24 belonged to several different functional categories such as structural molecule activity, extracellular regions, structural formation, cell death, biological adhesion, developmental processes, locomotion, and biological regulation that were associated with cancer. The remaining 10 genes were not involved in cancer research. Of these genes, the expression levels of Matrix metalloproteinase-12 (MMP12), Caspase-associated recruitment domain 14 (CARD14), and Chitinase 3-like 1 (CHI3L1) were confirmed by semi-quantitative RT-PCR. A two-way clustering algorithm divided the 36 samples into three categories and the overall correct classification efficiency was 80.6% (29/36). Almost all of these genes (31/34) showed constant changes in the process of normal gastric epithelial cells to mGED to gastric cancer.


CONCLUSIONS
The results of this study provided global gene expression profiles during the development and progression from normal gastric epithelial cells to mGED to gastric cancer. These data may provide new insights into the molecular pathology of gastric cancer which may be useful for the detection, diagnosis, and treatment.
Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200092, China.
Mao-Lan
ML
Li
Jing-Cheng
JC
Zhang
Song-Gang
SG
Li
Wen-Guang
WG
Wu
Long-Hua
LH
Rao
Ping
P
Dong
Jun
J
Gu
Jian-Hua
JH
Lu
Lin
L
Zhang
Qi-Chen
QC
Ding
Xiang-Song
XS
Wu
Jia-Sheng
JS
Mu
Jia-Hua
JH
Yang
Wen-Jie
WJ
Zhang
Lei
L
Chen
Ying-Bin
YB
Liu
D000328:Adult; D000368:Aged; D004847:Epithelial Cells / Q000378:metabolism*; D005753:Gastric Mucosa / Q000378:metabolism* / Q000473:pathology*; D006801:Humans; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013270:Stomach / Q000473:pathology*; D013274:Stomach Neoplasms / Q000235:genetics*; D059467:Transcriptome / Q000235:genetics*