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Exploiting Urine RNAs as Diagnostic Markers of Bladder Cancer

Computed tomography (CT) scan of the bladder showing bladder cancer (arrow). Credit: Dr. Peter Choyke/ Molecular Imaging Program

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Oncotarget published "Transcriptome analyses of urine RNA reveal tumor markers for human bladder cancer: validated amplicons for RT-qPCR-based detection" which reported that in case of bladder cancer, urine RNA represents an early potentially useful diagnostic marker.

Here the authors describe a systematic deep transcriptome analysis of representative pools of urine RNA collected from healthy donors versus bladder cancer patients according to established SOPs.

This analysis revealed RNA marker candidates reflecting coding sequences, non-coding sequences, and circular RNAs.

Next, they designed and validated PCR amplicons for a set of novel marker candidates and tested them in human bladder cancer cell lines.

This Oncotarget work strongly suggests exploiting urine RNAs as diagnostic markers of bladder cancer and it suggests specific novel markers.

Dr. Georg Sczakiel from The Universität zu Lübeck and UKSH, said "Human bladder cancer (BCa) is one of the most common cancer types in humans."

With regard to BCa, RNA markers have been studied by transcriptome analyses of single cells, tissue samples and urine.

In case of BCa, urine is thought to be the most promising source for RNA-based tumor markers as direct physical contact between tumor cells and urine seems to be given.

On the other hand, urine RNA samples contain RNAs which are suitable for cDNA synthesis and RT-qPCR detection.

Cell-free RNA contained in urine samples can be protected against degradation, i.e., stabilization of RNA markers is possible such that shipping of samples and storage is possible.

This consists of SOP-based acquisition of urine, stabilization of urine RNA, delivery and storage of samples, RNA preparation, and deep transcriptome analyses.

The Sczakiel Research Team concluded in their Oncotarget Research Output that while all of these hits focus on conventional linear transcripts the authors also noted experimental evidence supporting the existence of circular RNAs that seem to be able to monitor differences between the healthy state and the cancer state.

This is reflected by a number of recent studies describing a link between circular RNA and cancer.

However, such evidence derived from in silico analyses does not necessarily prove that such circRNAs exist in reality.

A set of experimental evidence is necessary to sufficiently strongly verify their existence.

However, such assays go beyond the scope of this study although this is one promising way to proceed in order to identify new and potent RNA markers.

Reference: Dubois J, Rueger J, Haubold B, Far RK-K, Sczakiel G. Transcriptome analyses of urine RNA reveal tumor markers for human bladder cancer: validated amplicons for RT-qPCR-based detection. Oncotarget. 2021;12(10):1011-1023. doi: 10.18632/oncotarget.27954

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