Abstract
microRNAs (miRNAs) are small noncoding RNAs and promising cancer biomarkers. Prostate-specific antigen (PSA) testing revolutionized prostate cancer (PCa) diagnostics and monitoring. However, PSA testing also contributes to PCa overdiagnoses that are detrimental on patients' health and may lead to overtreatment. Here, we searched for circulating miRNAs that could serve as biomarkers facilitating differentiation between PCa and benign prostate hyperplasia (BPH). 66 patients with PCa or BPH were investigated (33 patients in each cohort). Men with PCa underwent minimally invasive radical prostectomy (RP), whereas men with BPH underwent either holmium laser enucleation of the prostate (HOLEP), transurethral resection of the prostate (TURP) or simple prostatectomy. We performed RNAseq of PCa and BPH serum samples, integrated our data with TCGA-PRAD cohort, followed by qPCR validation using independent cohort of PCa and BPH patients. RNAseq detected 295 miRNAs in serum samples, including 283 miRNAs that were both expressed by PCa tissues and present in PCa sera. 10 miRNAs were selected for qPCR validation. Expression of serum miR-1-3p, miR-96-5p, miR-148a-3p, and miR-375-3p was decreased in PCa patients when compared to BPH samples. Diagnostic accuracy of combinations of PSA with geometric means of [miR-1-3p, miR-148a-3p], [miR-148a-3p, miR-375-3p], and [miR-375-3p, miR-96-5p] exceed diagnostic value of PSA alone, with the top AUC 0.97 for [miR-1-3p, miR-148a-3p]/PSA (cut-off < 0.002893, sensitivity 95.83 %, specificity 91.30 %). In conclusion, we found a miRNAs that can support PCa diagnosis.
Published Version
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