Panel of 6 microRNAs for minimally invasive diagnosis of prostate cancer
INTRODUCTION AND OBJECTIVES: Routine screening of prostate cancer (PC) based on serum prostate-specific antigen detection and digital rectal examination has modest positive and negative predictive value. The aim of represented study was to identify a panel of plasma microRNAs (miRNAs) for minimally invasive diagnosis of PC.
METHODS: During 2014-2015, 245 patients participated in the cross-sectional study. The Group 1 consisted of 188 patients with histologically confirmed PC. The Group 2 consisted of 57 patients including healthy individuals and patients with benign prostatic hyperplasia, urinary system diseases or anomalies, bladder or renal cancer. Plasma miRNAs profiles was studied with aid of GeneChip’ miRNA 4.0 Arrays (Affymetrix, USA) comprising probe set for 2,578 human mature miRNAs. All miRNAs with the 3rd quartile of Bi-weight Average Signal (log2) less than 1,49 were excluded from the analysis just as miRNAs with signal correlating with hemoglobin level as hemolysis sign (p-value < 0.05 for Spearman rank correlation coefficient). SVM-based approach was used for development of a diagnostic classifier based on circulating miRNAs. Exhaustive analysis was performed for pairs and triplets of miRNAs with sensitivity, specificity and AUC calculation. Experiment have been conducted in accordance with the principles of the Declaration of Helsinki of World Medical Association.
RESULTS: Diagnostic significance was demonstrated even for pairs of miRNAs. In particular best pair consisting of hsa-miR155-5p and hsa-miR-619-5p allowed achieving 80.7% sensitivity at 69.2% specificity (AUC 0.817). Triplets of miRNAs showed better accuracy, e.g. for triplet hsa-miR-155-5p, hsa-miR-619-5p, and hsamiR-6777-5p sensitivity was 78.9% while specificity was 80.8% (AUC 0.850). The best triplet hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR-6886-5p allowed achieving 81.3% sensitivity at 80.8% specificity (AUC 0.860). For diagnostic panel consisting of all 6 miRNAs sensitivity reached 83.7% at specificity 84.6% (AUC 0.913).
CONCLUSIONS: These results show high diagnostic potential of the panel of 6 circulating miRNAs (hsa-miR-155-5p, hsa-miR-619-5p, hsa-miR-6777-5p, hsa-miR-6085, hsa-miR-6511b-5p, and hsa-miR6886-5p) for minimally invasive diagnosis of prostate cancer which may improve the diagnostic accuracy of modern PC screening.