Gene-Transcript Expression in Urine Supernatant and Urine Cell-Sediment Are Different but Equally Useful for...

Area of Science:

• Urology
• Molecular Diagnostics
• Oncology

Background:

• Urine is a promising non-invasive liquid biopsy for prostate cancer (PCa) detection.
• PCa-specific transcripts, like the TMPRSS2:ERG fusion gene, are present in urine extracellular vesicles (EVs) and cell sediment (Cell).
• The comparative utility of these urine fractions for PCa detection requires further elucidation.

Purpose of the Study:

• To investigate the relative usefulness of gene expression in urine EVs and Cell fractions for PCa detection.
• To identify specific gene panels within each fraction that are indicative of PCa.
• To determine if fractionating urine improves diagnostic accuracy for PCa.

Main Methods:

• Urine samples from 76 men (40 PCa, 36 non-cancer) were analyzed using NanoString for 154 PCa-associated genes.
• Differential gene expression analysis was performed comparing EV and Cell fractions.
• Boruta analysis was employed to identify informative gene panels for PCa detection in each fraction.

Main Results:

• Differential gene expression analysis revealed 57 gene-probes significantly higher in EVs and 26 in Cells (p < 0.05).
• Prostate-specific genes (KLK2, KLK3) were ~20x higher in EVs, while PTPRC (white blood cells) was ~1000x higher in Cells.
• Boruta analysis identified 11 gene-probes useful for PCa detection, with distinct panels for EVs (e.g., TMPRSS2:ERG) and Cells (e.g., OR51E2).

Conclusions:

• Fractionating whole urine into EVs and Cell components prior to analysis is beneficial for PCa detection.
• Distinct sets of gene-probes are informative in EVs and Cell fractions, suggesting a synergistic diagnostic approach.
• Neither fraction alone provided superior information, highlighting the value of analyzing both for comprehensive PCa detection.