Abstract
77 Background: Gastric cancer (GC) is the fourth leading cause of cancer-related death in the world. Some gastric adenomas may progress to adenocarcinoma in a short time. Several studies have examined adenomas the intermediate step of gastric carcinoma development. MicroRNAs have an important role in progression of gastric cancer but less is known about their role in premalignant adenomas. Changes in the expression pattern of miRNAs can be informative and highly significant in the gastric adenoma-carcinoma sequence progression as well. However, to date precancerous lesions (such as adenomas) have been investigated less frequently than cancers compared to healthy tissues. The aim of the present study was to perform a miRNA microarray analysis of normal, low-grade dysplasia, and high-grade dysplasia using fresh frozen tissues. Changes in miRNA expression patterns were also verified from samples obtained from the same patients using TaqMan MicroRNA Assays. Methods: Human tissue samples were obtained from nine patients who underwent endoscopic submucosal dissection (ESD) due to gastric adenoma or early gastric cancer at Severance Hospital of Yonsei University. Tumor and non-tumor mucosa tissue in each patient were taken just before ESD using biopsy forceps and frozen in the nitrogen tank. The miRNA expression profiles were analyzed by Affymetrix Gene-Chip miRNA 4.0 array (Homo sapiens). qRT-PCR was performed using TaqMan MicroRNA Assays (Applied Biosystems). Results: There were 28 (up-regulation) and 10 (down-regulation) miRNAs which showed significantly different expression between control group and low-/high-grade dysplasia group. miRNAs showing altered expression in normal and low-/high-grade dysplasia by microarrays were selected, and the expression tendencies were detected by real-time PCR validation. Three miRNAs (miR-421, miR-29b-1-5p, miR-27b-5p) were selected the continually upregulated from normal to low-/high-grade dysplasia based qRT-PCR in tissue samples. Conclusions: We identified new, less known miRNAs (miR-421, miR-29b-1-5p, miR-27b-5p), with altered expression in different grade dysplasia compare with normal samples.
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