A comparison of MicroRNA profiles in the circulating cells from men with locally confined and advanced prostate cancer


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Geetha Laxala1, Freddie Hamdy2, Stephane Larre2, James Catto1

1University of Sheffield, UK, 2University of Oxford, UK

Abstract

Background
New methods are required to accurately stage prostate cancer as up to 50% of men develop distant metastases after radical local treatment. Various data suggest that prostatic tumour cells are found in the peripheral circulation of men with the disease and their concentration is proportional to tumour burden. For example, we have previously shown that the detection of aberrant hypermethylation for relative-prostate specific loci such as GSTP1 can detect circulating prostatic cells. The expression of prostate specific microRNA has recently been described. Here we examine microRNA profiles in circulating blood cells from men with local and advanced prostate cancer.

Method
We developed protocols to extract small RNA from peripheral circulation cells and profiled the expression of 365 microRNAs in 6 men with metastases and 6 with localised prostate cancer using Taqman microfluidic cards. We then used multiplexed quantified rtPCR (Taqman) to determine the expression of selected microRNAs in 60 men (40 with advanced (mean PSA=97ng/ul, cT3/4/M1, Gleason 7-10 and 20 with localised cancer (mean PSA=6.3ng/ul, cT1c, Gleason 6).

Results
Profiling microRNA expression in the initial 12 men revealed numerous differentially expressed microRNAs. These included microRNA reported as aberrantly expressed in primary prostate tumours such as miR-96, miR-15a and miR-518b. We selected 10 microRNA to evaluate in the larger cohort and found miR-21 and miR-183 to be associated with the presence of localised disease (T Test P<0.007, AUROC 0.84 and 0.80, respectively).

Conclusion
Our data suggest that microRNA expression may be used to detect either circulating prostate cancer cells or reactive lymphocytic changes that could be used to stage prostate cancer. We are currently expanding our second cohort to a total of 100 cases (matched sample sizes) and 20 men with no prostate cancer (two negative trans-rectal biopsies).

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