Analysis of blood-derived circulating microvesicles for microRNA biomarkers of metastatic and nonmetastatic prostate cancer.
Hamdy FC., Bryant RJ., Pawlowski TL., Marsden G., Smith S., Vessella R., Kuslich CD.
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.