Abstract
203 Background: MicroRNAs (miRNA) are small, noncoding nucleic acids that regulate expression of genes. Altered expression of miRNA has been implicated as a factor in carcinogenesis. We previously demonstrated 27 miRNA with differential expression that varied greater than two-fold between areas of benign and cancerous prostate glands in 64 patients. The goal of this study was to validate these findings in a selected group. Methods: RNA was extracted from prostate cancer foci and areas of benign glands from paraffin embedded prostatectomy specimens from 29 selected patients. Five patients each were selected with Gleason 3+3, 3+4, 4+3, and 4+4 or higher. The remaining nine selected patients went on to develop metastatic disease. Expression profiles for 577 miRNA were analyzed using Taqman OpenArray. Data analysis was performed using the mean-centering method for normalizing miRNA across the original and validation cohorts. Results: Significant overlap was found between the original and validation cohorts for miRNA that were upregulated at least two-fold between benign and cancerous glands (p<0.05). There were no differences in miRNA expression between T2 and T3 cases. Comparison of Gleason 6 vs Gleason 8+ showed significant difference in expression of mir-185, mir106b, and mir-181a. Interestingly, among the subset of patients that developed metastatic disease, the benign prostate glands demonstrated significant overexpression of mir-21 as compared to the benign glands of the localized cohort. Mir-21 is a known oncomir shown to be overexpressed in other metastatic tumors. Conclusions: This study validates our findings on differential expression of miRNA between cancerous and benign glands. There was a significant difference in expression of three miRNAs between Gleason 6 and 8 cancers, and no differences were found between T2 and T3. miRNA may represent a unique signature in the benign glands of patients with metastatic disease.
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