J Cancer 2020; 11(15):4542-4549. doi:10.7150/jca.45077

Research Paper

Circulating let-7f-5p improve risk prediction of prostate cancer in patients with benign prostatic hyperplasia

Yuqiu Ge1*✉, Qiangdong Wang2,3*, Wei Shao4*, You Zhao5, Qianqian Shi5, Qinbo Yuan2,3✉, Li Cui5✉

1. Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, China.
2. Department of Urology, Huaiyin Hospital of Huai'an City, Huai'an, China.
3. Department of Urology, Huaiyin People's Hospital of Huai'an City, Huai'an, China.
4. Department of Science and Technology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, China.
5. Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China.
*These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Ge Y, Wang Q, Shao W, Zhao Y, Shi Q, Yuan Q, Cui L. Circulating let-7f-5p improve risk prediction of prostate cancer in patients with benign prostatic hyperplasia. J Cancer 2020; 11(15):4542-4549. doi:10.7150/jca.45077. Available from http://www.jcancer.org/v11p4542.htm

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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 biopsy. The area under the receiver operating characteristic curve (AUC) was conducted to evaluate the diagnostic efficacy of miRNAs and PSA.

Results: 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 AUC was 0.904 for combination of lef-7f-5p and PSA, which 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 predictive accuracy of PCa.

Conclusions: Our study suggests that plasma let-7f-5p combining PSA could serve as potentially diagnostic biomarkers for PCa.

Keywords: microRNA, prostate cancer, benign prostatic hyperplasia, diagnostic biomarker