Large-scale circulating microRNA profiling for the liquid biopsy of prostate cancer

Purpose: The high false-positive rate of prostate-specific antigen (PSA) may lead to unnecessary prostate biopsies. Therefore, the United States Preventive Services Task Force recommends that decisions regarding PSA-based screening of prostate cancer (PCa) should be made with caution in men aged 55-69 years, and that men ≥70 years should not undergo PSA screening. Here, we investigated the potential of serum microRNAs (miRNAs) as an accurate diagnostic method in patients with suspected prostate cancer (PCa). Experimental Design:Serum samples of 809 patients with PCa, 241 negative prostate biopsies, and 500 patients with other cancer types were obtained from the National Cancer Center, Japan. Forty-one healthy control samples were obtained from two other hospitals in Japan. Comprehensive microarray analysis was performed for all samples. Samples were divided into three sets. Candidate miRNAs for PCa detection were identified in the discovery set (n=123). A diagnostic model was constructed using combinations of candidate miRNAs in the training set (n=484). The performance of the diagnostic model was evaluated in the validation set (n=484). Results: In the discovery set, 18 candidate miRNAs were identified. A robust diagnostic model was constructed using the combination of two miRNAs (miR-17-3p and miR-1185-2-3p) in the training set. High diagnostic performance with a sensitivity of 90% and a specificity of 90% was achieved in the validation set regardless of the Gleason score and clinical TNM stage. Conclusions: The model developed in the present study may help improve the diagnosis of PCa and reduce the number of unnecessary prostate biopsies.

https://ift.tt/2GRxsa3