MicroRNAs and Colon and Rectal Cancer: Differential Expression by Tumor Location and Subtype

MicroRNAs are thought to have an impact on cell proliferation, apoptosis, stress responses, maintenance of stem cell potency, and metabolism and are, therefore, important in the carcinogenic process. In this study, we examined 40 colon tumors, 30 rectal tumors, and 30 normal tissue samples (1 0 proximal colon, 10 distal colon, and 10 rectal paired with cancer cases) to examine miRNA expression profiles in colon and rectal tumors. MiRNA expression levels were adjusted for multiple comparisons; tumor tissue was compared with noncancerous tissue from the same site. A comparison of normal tissue showed 287 unique miRNAs that were significantly differentially expressed at the 1.5-fold level and 73 with over a two-fold difference in expression between colon and rectal tissue. Examination of miRNAs that were significantly differentially expressed at the 1.5-fold level by tumor phenotype showed 143 unique miRNAs differentially expression for microsatellite instability positive (MSI+) colon tumors; 129 unique miRNAs differentially expressed for CpG Island Methylator Phenotype positive (CIMP+) colon tumors; 135 miRNAs were differentially expressed for KRAS2-mutated colon tumors, and 139 miRNAs were differentially expressed for TP53-mutated colon tumors. Similar numbers of differentially expressed miRNAs were observed for rectal tumors, although the miRNAs differentially expressed differed. There were 129 unique miRNAs for CIMP+, 143 unique miRNAs for KRAS2-mutated, and 136 unique miRNAs for TP53-mutated rectal tumors. These results suggest the importance of miRNAs in colorectal cancer and the need for studies that can confirm these results and provide insight into the diet, lifestyle, and genetic factors that influence miRNA expression. (C) 2010 Wiley-Liss, Inc.