Gene Expression Profiling of Colonic Serrated Epithelial Lesions.
Terri S Giles, David Chiao, Edward Stelow, Patcharin Pramoonjago, Christopher A Moskaluk. University of Virginia, Charlottesville
Background: A subset of serrated epithelial lesions in the colon have been found to have an increased risk of malignant degeneration. These lesions have been termed sessile serrated adenomas or sessile serrated polyps (SSP) to distinguish them from hyperplastic polyps (HP) that have no or minimal risk of progression to carcinoma. Distinguishing SSPs from HPs may be problematic by histology, and finding distinguishing biomarkers may be of clinical utility.
Design: Histologic slides of serrated colonic epithelial lesions were reviewed and 10 consensus cases each of SSPs and HPs were selected. Corresponding tissue from the paraffin blocks was dissected, RNA was extracted and was screened for integrity using a quantitative RT-PCR analysis. Passing RNA samples were reverse transcribed, subjected to linear cDNA amplification and assayed on Affymetrix U133 Plus 2 oligonucleotide microarrays.
Results: 3 cases each of the SSP and HP cohort contained RNA of sufficient quality to be assayed by microarrays. The fluorescence intensity data was subjected to a metric that ranked genes on the basis of fold difference, absolute difference and statistical significance. The top 5 probes sets corresponding to annotated genes that distinguish SSPS from HPs are: MUC5AC, CYP2C18, PLA2G16, TMEM92 and BHMT2. The top 5 genes that distinguish HPs from SSPs are: MUC12, EXOC3, IGHA1, MS4A12 and SELENBP1. The table shows the probe designation, the gene name, the average fluorescence intensity for the SSP and HP samples, the fold change between SSP and HP samples and the P value (2 tailed t-test).
|Probe Set||Gene||SSP - Avg||HP - Avg||SSP/HP||P|