Distinctive Pattern of Gene Expression in Intestinal and Diffuse Gastric Cancer on cDNA Microarray

ABSTRACT

Molecular investigations have provided evidence of the involvement of multiple genetic alterations in gastric carcinogenesis. Regarding the clinical, epidemiological and genetic aspects, well and poorly differentiated gastric adenocarcinoma exhibit some differences.(1) PURPOSE: To examine the gene expression profile of stomach cancer and evaluate the differentially expressed genes between intestinal and diffuse cancer type. METHODS: Five intestinal and 5 diffuse type gastric cancer tissues and their matched normal mucosa were obtained from patients who underwent a gastrectomy. The mRNAs frome these tissues were extracted, reverse transcribed with simultaneous Cy3 and Cy5 labeling, and hybridized with the MAGIC(TM) microarray (Korean 4.6k chip). The chip was scanned using Generation III, image analysis with Imagine 5.0 and data analysis with Arraytool, R, and SAM. RESULTS: Twelve and 15 genes were found to be up- and down-regulated genes in the intestinal type, whereas these figures were 25 and 4 genes in the diffuse type, respectively. With the intestinal and diffuse type, 2 and 9, 10 and 4 exhibites up- and down-regulation greater than 2 fold, respectively. In the intestinal type genes, up-regulation was associated with metabolism, cell growth and cell communication; whereas, down-regulation was associated with metabolism and mainly unclassified functions. In the diffuse type genes, up-regulation was associated with metabolism, cell growth, cell communication and drug resistance, ; whereas, down-regulation was associated with metabolism and cell growth. Non-hierarchical clustering of the genes revealed two expression profiles, which can be used to classify the above 10 samples into two exactly distinct types. CONCLUSION: The analysis of the intestinal and diffuse gastric cancers using the cDNA microarray showed distinct gene expression profiles, consistent with their different histological and clinical features.