Expression Profiling of circulating micro-RNAs in Prostate Cancer
Kelly, Brian Daniel
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Mi(cro)RNAs are small non-coding RNAs whose differential expression in tissue has been implicated in the development and progression of many malignancies, including prostate cancer. The discovery of miRNAs in the blood of patients with a variety of malignancies makes them an ideal, novel biomarker for prostate cancer diagnosis. The aim of this study was to identify a unique expression profile of circulating miRNAs in patients with prostate cancer attending a rapid access prostate assessment clinic. To conduct this study blood and tissue samples were collected from 102 patients (75 with biopsy confirmed cancer and 27 benign samples) following ethical approval and informed consent. These patients were attending a prostate assessment clinic. Samples were reverse-transcribed using stem-loop primers and expression levels of each of 12 candidate miRNAs were determined using real-time quantitative PCR. MiRNA expression levels were then correlated with clinicopathological data and subsequently analysed using qBasePlus software and Minitab. Circulating miRNAs were detected and quantified in all subjects. The analysis of miRNA mean expression levels revealed that 4 miRNAs were significantly dysregulated, including let-7a (p=0.005) which has known tumour suppressor characteristics, along with miR-141 (p=0.01) which has oncogenic characteristics. In 20 patients undergoing a radical retropubic-prostatectomy, the expression levels of miR-141 returned to normal at day 10 post-operatively. A panel of 4 miRNAs could be used in combination to detect prostate cancer with an AUC of 0.783 and a PPV of 80%. These findings identify a unique expression profile of miRNA detectable in the blood of prostate cancer patients. This confirms their use as a novel, diagnostic biomarker for prostate cancer.