Non-coding RNAs as biomarkers in liquid biopsies with a special emphasis on extracellular vesicles in urological malignancies

ABSTRACT

Introduction: Non-coding RNAs (ncRNAs) are important regulators of cellular signaling in tumor-related processes. They can not only be detected in tumor tissues, but also in body fluids. ncRNAs are released into circulation as cell-free RNAs in at least two ways: bound to proteins like Ago2 or packed in extracellular vesicles (EV). Therefore, they have a great potential to serve as biomarkers in liquid biopsies. This review gives an overview of the current knowledge concerning ncRNAs and EVs as putative liquid biomarkers in urological tumor diseases.

Areas covered: Literature was searched for ncRNAs including microRNA, long non-coding RNA, small interfering RNA, small nuclear RNA, small nucleolar RNA and PIWI-interacting RNA in blood (serum, plasma) and urine samples from urological tumor (urothelial, kidney, prostate, testicular germ cell, penile cancer) patients.

Expert opinion: The data demonstrate an important potential of circulating non-coding RNAs as biomarkers in liquid biopsies for diagnosis and follow-up of patients with urological tumors. To translate these markers into clinical practice, independent and prospective validation, standardization of isolation and quantification techniques are inevitable. Another task is the development of predictive ncRNA biomarkers to overcome problems associated with tumor heterogeneity and to select patients individually for systemic therapies.

KEYWORDS:

• Non-coding RNA
• microRNA
• long non-coding RNA
• PIWI-interacting RNA
• liquid biopsy
• bladder cancer
• renal cell carcinoma
• prostate cancer
• testicular germ cell tumors
• upper urinary tract urothelial cancer
• extracellular vesicle
• exosome
• biomarker

Article highlights

• Non-coding RNAs from liquid biopsies become more and more relevant to increase the diagnostic accuracy in urological tumors.

• Most studies investigated miRNAs, only some focused on lncRNAs.

• Standardization of isolation and quantification of miRNAs and lncRNAs as well as independent prospective testing are inalienable tasks in order to translate these putative biomarkers into clinical practice.

• Non-coding RNAs from liquid biopsies have the potential to improve individual systemic therapy selection although data on this topic are still limited.

• EVs represent a new source of biomarkers including EV-packed non-coding RNAs.

• Strategies to enrich tumor-specific EVs could increase diagnostic accuracy compared to the whole cell-free ncRNA fraction from serum, plasma or urine.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This paper was not funded.