Gene profiling of colonic serrated adenomas by using oligonucleotide microarray

Abstract

The serrated pathway has been proposed as an important concept explaining the colorectal carcinogenesis. However, the key molecules of the serrated pathway which contribute to the formation of serrated polyp are still poorly understood. To elucidate the molecular genetic basis of the serrated pathway, we performed an initial oligonucleotide microarray to analyze the gene expression pattern of patients with colonic serrated adenomas. Oligonucleotide microarrays containing 3,096 genes were used to compare individual gene profiles of serrated adenoma samples (n = 5) and normal mucosal samples obtained from colon in patients by colonoscopy. Three genes were further investigated by means of quantitative reverse transcription polymerase chain reaction (RT-PCR) for validation. The Significance Analysis of Microarray (SAM) package method was used to identify differentially expressed genes. Compared with normal colonic mucosa tissue, 73 genes were upregulated at least twofold, and 51 genes were downregulated by at least 50% in serrated polyp samples (approximately 3.6% of genes evaluated) with a p-value of less than 0.05. Moreover, some of the gene expression patterns observed were similar to those of previously reported in colorectal cancer, suggesting reinforcement of tendency to malignancy. Three genes (TNFRSF10A, BENE, RARA) with strongly significant expression intensities in the oligonucleotide microarray results were validated by quantitative RT-PCR. TNFRSF10A had upregulated expression patterns while BENE, RARA had downregulated expression pattern. Although our report presents only preliminary results, we think they provide important data regarding serrated adenomas not only to better define the precise mechanism of genetic changes involved as the main member in serrated pathway of colorectal carcinogenesis but also to yield practical information for identifying optimized diagnostic modalities.