[783] Differential MicroRNA Expression in Localised and Advanced Prostatic Adenocarcinoma

C Barrett, P Smyth, A Murphy, B Loftus, O Sheils, JJ O'Leary. Trinity College Dublin, Dublin, Ireland; Adelaide & Meath Hospital, Dublin, Ireland

Background: MicroRNAs (miRNAs) are a group of small non-coding RNAs that negatively regulate gene expression by targeting mRNAs for cleavage or translational repression. Unique miRNA expression profiles have been able to subclassify various tumors. We hypothesise that distinctive miRNA expression profiles exist in localised (LC) and advanced (AC) prostate cancer, which may be important indicators of disease progression.
Design: Using FFPE material, total RNA was extracted from Gleason grade 3 areas of 5 LC and 4 AC cases of PCa (Gleason score 6 and Gleason score 7 respectively) and 4 control cases of benign prostatic hyperplasia (BPH). Extractions were carried out with Ambion RecoverAll - Total Nucleic Acid Extraction Isolation Kit. Using TaqMan low density arrays [TLDAs], examining the profile of 380 miRNA molecules, TaqMan RT-PCR was carried out in duplicate to examine global regulatory miRNA expression of the sample cohort. Analysis of relative RNA expression data was performed using the 2- Δ Δ Ct method. Statistical comparison between sample cohorts was performed using the t-test.
Results: There was significant (p<0.05) differential expression of the following miRNAs:

DIFFERENTIAL EXPRESSION OF miRNAs
miRNA p-value Status of miRNA
miR-28-5p0.041Downregulated
let-7c0.027Downregulated
miR-930.018Upregulated
miR-15a0.010Downregulated
miR-23b0.002Downregulated
LC v BPH



DIFFERENTIAL EXPRESSION OF miRNAs
miRNA p-value Status of miRNA
miR-19a0.048Downregulated
miR-310.048Downregulated
let-7a0.036Downregulated
miR-27b0.034Downregulated
miR-10a0.024Downregulated
miR-15a0.020Downregulated
miR-10.017Downregulated
miR-250.004Downregulated
miR-23b0.004Downregulated
miR-28-5p0.002Downregulated
AC v BPH

There was significant (p-value: 0.002) downregulation of miR-31 in cases of AC v LC.
Conclusions: Overrepresentation of potential pathways affected by these upregulated/downregulated miRNAs include cell cycle, cell signalling, cell differentiation, apoptosis, DNA repair, hormone activity, inflammatory response and lipid metabolism. LC and AC have distinctive miRNA regulatory expression profiles relative to each other and relative to BPH. These up/down regulated miRNAs may have a role in the pathogenesis and progression of prostate cancer.
Category: Genitourinary (including renal tumors)

Tuesday, March 23, 2010 1:00 PM

Poster Session IV # 123, Tuesday Afternoon

 

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