Discovery and Validation of Serum MicroRNAs as Early Diagnostic Biomarkers for Prostate Cancer in Chinese Population

Prostate cancer (PCa) incidence has been rising in Chinese population. Current PSA-based biopsy has limited positive rate. Our research focused on development of serum markers for the diagnosis of PCa in patients with elevated PSA. miRNAs are found to be aberrantly expressed in many types of cancer. They are readily detectable in plasma and serum. Currently, miRNAs are being evaluated as potential prognostic and diagnostic tools for many types of cancer. We first profiled global serum miRNAs in a pilot set of PCa and benign prostatic hyperplasia (BPH) cases undergoing TRUS-guided prostate biopsy due to elevated PSA levels. A total of 20 differentially expressed miRNAs were discovered by high throughput microarray for further testing using qRT-PCR. In the training phase with 78 PCa and 77 BPH cases, miR-365a-3p, miR-4286, miR-424-5p, miR-27a-3p, and miR-29b-3p were found to have potential diagnostic value. The Logistics regression equation was established by 5 parameters including PSA, prostate volume, miR-4286, miR-27a-3p, and miR-29b-3p and ROC analysis of this model was made with AUC up to 0.892 (95% CI: 0.832-0.937, sensitivity 78.95%, and specificity 92.21%). The panel had excellent diagnostic performance and its significance was confirmed in 100 serum samples in the validation cohort. Overall, we found a panel of serum microRNAs that have considerable clinical significance in detecting early-stage prostate cancer. When combined with PSA and prostate volume, these microRNAs exhibit favorable diagnostic potency.