Circulating microRNA signature for the diagnosis of very high-risk prostate cancer

Significance

Serum microRNAs (miRNAs) have emerged as potential noninvasive biomarkers to diagnose prostate cancer (PCa), the most common noncutaneous malignancy among Western men. However, intermediate grades of PCa cannot be distinguished from aggressive forms using current miRNA signatures due to the heterogeneity of PCas. Recently, a high-throughput, spherical nucleic acid-based miRNA expression profiling platform, called the Scano-miR bioassay, was developed to measure the expression levels of miRNAs with both high sensitivity and specificity. By studying serum miRNAs of PCa using the Scano-miR bioassay, we identified a unique molecular signature specific for very high-risk aggressive PCa. This molecular signature will assist in differentiating patients who may benefit from therapy from those who can be closely monitored on active surveillance.

Abstract

We report the identification of a molecular signature using the Scano-miR profiling platform based on the differential expression of circulating microRNAs (miRNA, miR) in serum samples specific to patients with very high-risk (VHR) prostate cancer (PCa). Five miRNA PCa biomarkers (miR-200c, miR-605, miR-135a*, miR-433, and miR-106a) were identified as useful for differentiating indolent and aggressive forms of PCa. All patients with VHR PCa in the study had elevated serum levels of miR-200c. Circulating miR-433, which was differentially expressed in patients with VHR versus low-risk (LR) forms of PCa, was not detectable by quantitative real-time PCR in samples from healthy volunteers. In blind studies, the five miRNA PCa biomarkers were able to differentiate patients with VHR PCas from those with LR forms as well as healthy individuals with at least 89% accuracy. Biological pathway analysis showed the predictive capability of these miRNA biomarkers for the diagnosis and prognosis of VHR aggressive PCa.