Abstract 5033: Relationship between microRNA expression and Gleason grading system in prostate cancer

Abstract

Abstract Background: Recent studies have shown that some microRNA (miRNA) expression profiles are associated with clinicopathological findings, including “Gleason score (GS)” in human prostate cancer (PC). However, the direct relationship between “Gleason pattern (GP)” and miRNA expression remains unclear. In this study, we investigated the miRNA expression profile in each GP (GP 3, GP 4, and GP 5). Methods: Formalin-fixed, paraffin-embedded (FFPE) tissue samples obtained from radical prostatectomy (patient set 1, n = 43, including [GP 3] n = 22, [GP 4] n = 35, and [GP 5] n = 12) and prostate needle biopsy (patient set 2, n = 9, [GP 4] n = 9) were used. Cancer tissues and adjacent normal counterparts were collected separately using laser-captured microdissection with subsequent isolation of total RNA. Real time reverse transcription polymerase chain reaction (RT-PCR) was performed to determine the relative expression of miRNAs, including miR-31, -34c, -96, -182, -183, -205, -221, and miR-222, which are currently reported to be involved in the progression of PC. Results: In the radical prostatectomy samples (patient set 1), relative expression (mean ± SE) of miR-31, miR-34c, and miR-205 in every GP was significantly decreased (miR-31: [GP 3] 0.028 ± 0.007, [GP 4] 0.047 ± 0.017, and [GP 5] 0.071 ± 0.022; miR-34c: 0.208 ± 0.066, 0.419 ± 0.219, and 0.210 ± 0.054; and miR-205: 0.021 ± 0.008, 0.015 ± 0.003, and 0.050 ± 0.023, all p-values < 0.01) compared to normal counterparts. However, there was no significant difference between GP 3, GP 4, and GP 5. Meanwhile, in GP4, expression of miR-31, miR-182, and miR-205 in tissues obtained from high-grade cancer (GS 8 or GS 9) were significantly higher than those in tissues obtained from intermediate-grade cancer (GS 7) (miR-31: [high grade] 0.071 ± 0.027, [intermediate grade] 0.011 ± 0.003, p = 0.040; miR-182: 1.745 ± 0.278, 0.864 ± 0.136, p = 0.021; and miR-205: 0.022 ± 0.005, 0.005 ± 0.002, p = 0.002, respectively). Validation testing of biopsy samples (patient set 2) revealed that the relative expression of miR-182 was similarly and significantly higher in high-grade cancer tissue (high grade: 1.863 ± 0.381, intermediate grade: 0.717 ± 0.196, p = 0.043). Conclusion: The expression of miR-182 differed by cancer grade even in the same GP 4, and this difference was detected in both biopsy and radical prostatectomy samples. Our findings suggest that evaluations of miRNA expression with respect to Gleason grading in biopsy samples may contribute to more accurate preoperative cancer risk evaluation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5033. doi:1538-7445.AM2012-5033