A four-miRNA serum panel as a diagnostic biomarker for prostate cancer: an exploratory and validation study.

Background: Prostate-specific antigen (PSA) is widely used for prostate cancer (PC) screening, but its relatively low diagnostic accuracy may compromise early diagnosis and clinical management. There is an urgent need to identify convenient, cost-effective, and non-invasive diagnostic methods to reduce the rates of false positives and false negatives associated with PSA testing for prostate cancer. Serum miRNAs hold great promise as diagnostic tumor biomarkers. This study aimed to identify a novel serum miRNA panel for PC detection, with the goal of addressing the two major limitations of PSA: high false-positive and false-negative rates. Materials and methods: This study was conducted in three phases: biomarker screening, training, and validation. First, candidate miRNAs associated with prostate cancer were screened using the PubMed and ENCORI databases. Subsequently, real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to analyze miRNA expression in serum samples from the training group: 28 PC and 28 normal controls (NC), and the validation group: 84 PC and 84 NC, and to identify differentially expressed miRNAs. We assessed their diagnostic performance using receiver operating characteristic (ROC) curves and the area under the curve (AUC). We then constructed miRNA panel diagnostic models comprising different numbers of miRNAs to balance diagnostic performance and detection costs. Finally, bioinformatics analyses were performed to identify their target genes and functional pathways. Results: During the screening phase, 10 candidate miRNAs associated with PC were identified. In the training phase, 6 candidate miRNAs showed significant differential expression in PC compared with NC. In the validation phase, 5 candidate miRNAs (miR-101-3p, miR-154-5p, miR-199a-5p, miR-145-5p, and miR-30-5p) demonstrated favorable diagnostic performance for PC. After balancing diagnostic performance and detection costs, we ultimately selected the optimal 4-miRNA panel (miR-101-3p, miR-154-5p, miR-199a-5p, and miR-145-5p) as the final diagnostic biomarker panel for PC. This panel showed favorable diagnostic performance (AUC = 0.825, sensitivity = 83.33%, specificity = 69.05%). Bioinformatics analysis indicated that the Conclusion: A panel consisting of miR-101-3p, miR-154-5p, miR-199a-5p, and miR-145-5p exhibited excellent diagnostic efficacy for PC. This serum miRNA panel possesses translational potential and provides a novel strategy to address the two major limitations of PSA testing: high false-positive and false-negative rates. Clinical trial registration number: https://www.chictr.org.cn/showproj.html?proj=187882, identifier ChiCTR2200066840.