Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

4626 Background: Attempts to find a blood-based biomarker for prostate cancer (PCa) detection have been challenging. Quantification of microRNAs (miRs) in blood may identify potential genetic biomarkers. Using plasma-derived circulating microvesicles (cMV) as an enriched source of miRs from cells, we sought a miR biosignature that could distinguish PCa samples from healthy controls as well as a separate miR biosignature for metastatic PCa. METHODS: RNA was isolated from plasma-derived cMV from men with PCa (nonmetastatic and metastatic) and men with negative prostate biopsies. The samples were profiled for 750 miRs by a qRT-PCR panel. miRs with significant differences in expression were validated in larger sample sets using a TaqMan gene expression assay. RESULTS: Ten of 750 miRs compared in nonmetastatic PCa (n=64) and normal control (n=28) samples were found to have a >2.0-fold change with a P value <0.01. In a validation set (N=168), expression of 2 of the 10 miRs, hsa-miR-107 (P=0.03) and hsa-miR-574-3p (P=0.02), were significantly different between the nonmetastatic PCa (n=133) and control (n=35) samples. Comparison of metastatic (n=15) and nonmetastatic (n=55) samples found that 16 out of 750 miRs had a >2.0-fold change with a P value <0.01. Quantitation of these miRs in the subsequent validation set (39 metastatic and 73 nonmetastatic) found 6 of the 7 miRs tested validated (hsa-miR-200b, hsa-miR-375, hsa-miR-141, hsa-mir-331-3p, hsa-miR-181a, and hsa-miR-574-3p). In a separate cohort, hsa-miR-141 and hsa-miR-375 levels were significantly higher in cMV from the serum of metastatic PCa patients (n=47) than in cMV of nonrecurrent PCa patients (n=72; P=0.0001). CONCLUSIONS: Blood-derived cMV are a reliable source of miR for biomarkers. There was higher expression of 2 miRs in PCa samples than in controls. In metastatic plasma-derived cMV samples, there was higher expression of 7 miRs, and 2 of these (hsa-miR-141 and hsa-miR-375) were also found to be elevated in metastatic serum-derived cMV. These findings suggest the promise of a blood-based assay that utilizes the miR biosignatures of cMV for the detection of prostate cancer and identification of metastatic cases.

Type

Journal article

Journal

J clin oncol

Publication Date

20/05/2011

Volume

29