5690

MicroRNAs (miRNAs) are a class of small noncoding RNAs that control gene expression by targeting mRNAs and triggering either translation repression or RNA degradation. Several examples of an existing association between specific miRNAs and cancer were shown. In our study, we examined by chip microarray the expression of 245 miRNAs in 20 cases of human gastric carcinomas and matching normal gastric mucosa, each one had accurate follow-up. Microarray data were analyzed by using GenePixPro. Average values of the replicate spots of each miRNA were background-subtracted and normalized. Differentially expressed miRNAs were identified by using t test and significance analysis of microarrays (SAM). Results were validated by Real Time PCR and/or Northern Blot analyses. We identified a set of 7 differentially expressed miRNAs that are able to distinguish between normal and gastric cancer samples with a misclassification error of 17%. According to paired t-test analysis, five miRNAs are overexpressed in at least 85% of gastric cancer samples compared to control, namely miR-223 (2.77-fold increase), miR-25 (2.65-fold increase), miR-107 (1.97-fold increase), miR-24-2 (1.95-fold increase) and miR-181b (1.17-fold increase). Conversely, two miRNAs are downregulated in gastric cancer: mir-218-2 (0.56-fold increase) and miR-130b (0.78-fold increase), suggesting that both oncogenes and tumor suppressor genes might be regulated by miRNAs in gastric cancer. Interestingly, two distinct subgroups of patients clustered in both miR-223 and mir-25 analysis of expression: cluster # 1 (3.66-fold increase in miR-223; 3.65-fold increase in miR-25) and cluster # 2 (2.36-fold increase in miR-223; 2-fold increase in miR-25). Most notably, all controls in cluster # 1 showed typical hystological alterations associated with chronic gastritis while all controls in cluster # 2 were hystologically unremarkable. Chronic gastritis is a risk factor for gastric cancer and our results suggest that miR-223 and miR-25 altered expression may represent an early event in gastric tumorigenesis.

[Proc Amer Assoc Cancer Res, Volume 47, 2006]