Cancer Management and Research (Jan 2021)
Identification of Urinary Exosomal miRNAs for the Non-Invasive Diagnosis of Prostate Cancer
Abstract
Zhuo Li,1– 3,* La-Xiu Li,3,4,* Yan-Jun Diao,3 Juan Wang,3 Yun Ye,1,3 Xiao-Ke Hao2,3,5 1Department of Laboratory Medicine, The First Affiliated Hospital of Xi’an Medical University, Xi’an, Shaanxi 710077, People’s Republic of China; 2The National Engineering Research Center for Miniaturized Detection Systems, College of Life Science, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China; 3Department of Laboratory Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, Shaanxi 710032, People’s Republic of China; 4Department of Laboratory Medicine, Xi’an Fourth Hospital, Xi’an, Shaanxi 710004, People’s Republic of China; 5School of Medicine, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiao-Ke HaoSchool of Medicine, Northwest University, Xi’an, Shaanxi 710069, People’s Republic of ChinaEmail [email protected]: Novel and non-invasive biomarkers with higher sensitivity and specificity for the diagnosis of prostate cancer (PCa) is urgently needed. In this study, we used next-generation sequencing (NGS) to characterize the genome-wide exosomal miRNA expression profiling in urine specimens and explored the diagnostic potential of urinary exosomal miRNAs for PCa.Methods: Urinary exosomal microRNA expression profiling was performed by next-generation sequencing (NGS) and then validated by quantitative real-time PCR.Results: Significant downregulation of urinary exosomal miR-375 was observed in PCa patients compared with healthy controls, while the expression levels of urinary exosomal miR-451a, miR-486-3p and miR-486-5p were found to be significantly up-regulated in the PCa patients. Furthermore, the expression level of urinary exosomal miR-375 showed a significant correlation with the clinical T-stage and bone metastasis of patients with PCa (P< 0.05). Receiver operator characteristic curve demonstrated that the urinary exosomal miR-375, miR-451a, miR-486-3p and miR-486-5p levels can be used to differentiate PCa patients from healthy controls, with area under the curves (AUCs) of 0.788, 0.757, 0.704 and 0.796, respectively. The urinary exosomal miR-375 was found to be superior in discriminating between localized and metastatic PCa with an AUC of 0.806. Moreover, PCa patients can be distinguished from patients with benign prostatic hyperplasia by using a panel combining urinary exosomal miR-375 and miR-451a with an AUC of 0.726.Conclusion: These findings demonstrate that the urinary exosomal miRNAs can serve as novel and non-invasive biomarkers for diagnosing and predicting the progression of PCa.Keywords: prostate cancer, next-generation sequencing, urinary, exosomal miRNAs
