Circulating Let-7f-5p Improve Risk Prediction of Prostate Cancer in Patients with Benign Prostatic Hyperplasia

Background: Although the prostate-specific antigen (PSA) testing was widely used for early detection of prostate cancer (PCa), it is difficult for PSA to distinguish the PCa from benign prostatic hyperplasia (BPH) patients. Emerging evidence has shown that microRNA (miRNA) was a promising biomarker for PCa screening. Methods: We applied miRNA profiling from microarray or high-throughput sequencing in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to identify the differentially expressed miRNAs in PCa patients (n = 1,017) and controls (n = 413). Then, qRT-PCR analysis was used to validate the expression of candidate miRNAs in our independent cohort, include 66 PCa cases and 63 BPH patients diagnosed by needle biopsy. The receiver operating characteristic (ROC) curve and under the curve (AUC) were conducted to evaluate the diagnostic efficacy of miRNAs and PSA. Findings: In the microarray analysis, we identified two consistently differently expressed miRNAs (miR-103a-3p and let-7f-5p) between PCa patients and controls. In the subsequent qRT-PCR analysis, the let-7f-5p was upregulated in PCa compared with BPH patients (P=2.17E-07), but no statistically difference of miR-103a-3p expression was observed (P=0.456). The ROC analysis showed that the AUC of combination of lef-7f-5p and PSA (0.904) was significantly higher than that of let-7f-5p (0.782) or PSA (0.795) alone (P=7.55E-04 and P=2.09E-03, respectively). Besides, the results of decision curve analysis and nomogram prediction indicated that combination of let-7f-5p and PSA had superior clinical benefits. Interpretation: Our study suggests that plasma let-7f-5p combining PSA could serve as potentially diagnostic biomarkers for PCa. Funding Statement: This work was supported by the Natural Science Foundation of Jiangsu Province (BK20190600); The Fundamental Research Funds for the Central Universities (JUSRP11951); Public Health Research Center at Jiangnan University (JUPH201823). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: All of the subjects have written the informed consents. The Institutional Review Board of The Third Affiliated Hospital of Soochow University approved this study.