Plasma and urinary extracellular vesicles as a source of RNA biomarkers for prostate cancer in liquid biopsies

Abstract

Introduction: Extracellular vesicles (EVs) have emerged as a very attractive source of cancer- derived RNA biomarkers for the early detection, prognosis and monitoring of various cancers, including prostate cancer (PC). However, biofluids contain a mixture of EVs released from a variety of tissues and the fraction of total EVs that are derived from PC tissue is not known. Moreover, the optimal biofluid—plasma or urine—that is more suitable for the detection of EV- enclosed RNA biomarkers is not yet clear.Methodology: In the current study, we performed RNA sequencing analysis of plasma and urinary EVs collected before and after radical prostatectomy, and matched tumor and normal prostate tissues of 10 patients with prostate cancer.Results and Discussion: The most abundant RNA biotypes in EVs were miRNA, piRNA, tRNA, lncRNA, rRNA and mRNA. To identify putative cancer-derived RNA biomarkers, we searched for RNAs that were overexpressed in tumor as compared to normal tissues, present in the pre-operation EVs and decreased in the post-operation EVs in each RNA biotype. The levels of 63 mRNAs, 3 lncRNAs, 2 miRNAs and 1 piRNA were significantly increased in the tumors and decreased in the post-operation urinary EVs, thus suggesting that these RNAs mainly originate from PC tissue. No such RNA biomarkers were identified in plasma EVs. This suggests that the fraction of PC-derived EVs in urine is larger than in plasma and allows the detection and tracking of PC-derived RNAs.

sRNAflow: A Tool for the Analysis of Small RNA-Seq Data

“…The identification of differentially expressed small RNAs holds considerable diagnostic potential, particularly in cancer and cardiovascular diseases [ 6 , 7 , 8 , 9 , 53 ]. A preliminary iteration of the presented program has been utilised in recent publications focusing on the analysis of extracellular vesicle contents, engaging in discussions about the biological interpretations of the results [ 51 , 53 , 54 ].…”

Advances in Therapeutic Applications of Extracellular Vesicles

“… 148 Furthermore, lncRNA-Linc00662, lncRNA-CHASERR, and lncRNA-PCA3 were significantly elevated in the extracellular vesicles isolated from the urine of prostate cancer (PC) patients. 149 Plasma and urinary EVs as a potential sources of RNA biomarkers for prostate cancer in liquid biopsies.…”

Diagnostic value of urine cyclic RNA-0071196 for bladder urothelial carcinoma

“…It has been observed that the expression level of circular RNA in urine varies across multiple diseases, offering potential opportunities for circular RNA as a novel diagnostic and therapeutic approach. Unlike other sampling methods, urine collection is a noninvasive, painless, and highly convenient technique that enhances the accuracy and effectiveness of early disease diagnosis and treatment [ 10 ]. Urinary cytology test can be used as the gold standard for the diagnosis of bladder cancer, but this method has insufficient cell collection or improper treatment, which may lead to too low a number of cancer cells in the sample, making them difficult to detect and prone to false negatives [ 11 , 12 ].…”