Abstract

Emerging studies demonstrate that PIWI-interacting RNAs (piRNAs) are associated with various human cancers. This study aimed to evaluate the urinary extracellular vesicles (EVs) piRNAs as non-invasive biomarkers for prostate cancer (PCa) diagnosis. RNA was extracted from urinary EVs from five PCa patients and five healthy controls (HC), and the piRNAs were analyzed by small RNA sequencing. Dysregulated piRNAs were identified and then validated in another 30 PCa patients and 10 HC by reverse-transcription polymerase chain reaction (RT-qPCR). The expressions of novel_pir349843, novel_pir382289, novel_pir158533, and hsa_piR_002468 in urinary EVs were significantly increased in the PCa group compared with the HC group. The area under the curve (AUC) of novel_pir158533, novel_pir349843, novel_pir382289, hsa_piR_002468, and the combination of the four piRNA in PCa diagnosis was 0.723, 0.757, 0.777, 0.783, and 0.853, respectively. After the RNAhybrid program analysis, all four piRNAs had multiple potential binding sites with key mRNAs in PTEN/PI3K/Akt, Wnt/beta-catenin, or androgen receptor pathway, which are critical in PCa development and progression. In conclusion, our findings indicate that specific piRNAs in urinary EVs may serve as non-invasive diagnostic biomarkers for PCa.

Highlights

  • extracellular vesicles (EVs) have been traditionally considered as cellular rubbish, a simple means for disUrine biomarkers for non-invasive prostate cancer (PCa) diagnosis have been investigated over the posing unnecessary cellular waste products

  • It was not until the mid-1990s that EVs were years, and a few have been developed for clinical use including PCA3 [26], SelectMDx gradually exhibited as having a crucial role in intercellular communication, in normal physiological processes, and in the pathogenesis of disease, including cancer [31]

  • We investigated the EVs PIWI-interacting RNAs (piRNAs) profiles of PCa patients using small RNA sequencing combined with RT-qPCR validation

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Summary

Introduction

Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. PCa is one of the most common male urinary malignancies, with the highest morbidity and mortality among male malignancies in Europe and America [1]. PSA has greatly improved the proportion of patients diagnosed at localized /early stage, there are problems of overdiagnosis and overtreatment [2]. It is clear that there is a clinical need for improved PCa diagnostic biomarkers.

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