S1 Data -

Background
Prostate-specific antigen (PSA) is commonly used as a biomarker to diagnose and predict the course of prostate cancer (PCa). However, PSA detection is susceptible to changes in the physiologic environment, which may lead to some misdiagnosis. Thus, it is crucial to find a novel diagnostic marker.
Methods
We accessed microRNA (miRNA) expression datasets (GSE206793 and GSE112264) from the GEO database, analyzing peripheral blood samples from PCa patients. Differentially expressed miRNAs (DEmiRNAs) were identified using GEO2R. A specific miRNA, miR-455-3p, was pinpointed through rigorous analysis of clinical correlations and ROC curves. Peripheral blood samples from healthy individuals and PCa patients were subjected to qRT-PCR validation, aligning results with the GSE206793 dataset. The miRWalk database was utilized to predict downstream genes, while STRING facilitated the construction of a protein-protein interaction (PPI) network. KEGG pathway analysis enriched our understanding of potential molecular pathways.
Results
We found that miR-455-3p was highly expressed in the peripheral blood of PCa patients with Gleason score (GS) ≥ 8, while independent of T stage, age and PSA. ROC analysis revealed a favorable diagnostic efficacy of miR-455-3p and AUC for the two datasets was respectively 0.943 and 0.847. The qRT-PCR assay also revealed consistent results. Interestingly, the PSA levels of P1 (GS = 5 + 4) and P6 (GS = 3 + 3) were respectively 3.38 and 4.45 ng/ml, while miR-455-3p was highly expressed in both, suggesting its low misdiagnosis. The speculation was validated in GSE206793 dataset. Finally, 9 potential targets of miR-455-3p were predicted. PPI network revealed PPP2R2A, ITGB1 and CDKN1A as key nodes. KEGG pathway analysis revealed that they were enriched in various cancers, biological processes and molecular signals.
Conclusion
Our study identifies miR-455-3p as a promising diagnostic marker for PCa, outperforming PSA in terms of specificity and sensitivity. The robustness of miR-455-3p, coupled with its potential downstream targets and associated pathways, highlights its clinical significance for improved PCa diagnosis and management.