Genitourinary diseases, including cancers of the kidney and prostate, often require invasive biopsies for diagnosis due to limitations in existing clinical tools. Traditional urine tests, while useful for initial assessments, lack the detailed cell-type-specific information necessary for accurate diagnostics. In this study, researchers explored the potential of using cell-free RNA (cfRNA) in urine as a noninvasive biomarker for genitourinary diseases, aiming to replace or supplement current invasive methods.
Urine presents a promising diagnostic medium, as it directly interacts with genitourinary tissues and contains cfRNA and cellular by-products that reflect changes in tissue-specific gene expression. This study examined the urine transcriptome (the complete set of RNA transcripts) and metabolome to detect cell type-specific markers originating from genitourinary tissues, including the bladder, kidney, and prostate.
A significant challenge in cfRNA-based urine testing is the variability of solute concentration and the presence of confounding elements like bacteria or blood cells. The researchers addressed this by using a method that accounts for RNA library size variability, allowing for a more accurate reflection of cell type-specific signals.
The findings demonstrated that urine cfRNA measurements could distinguish cell types specific to genitourinary tissues, detecting changes in bladder and prostate cell markers. Notably, prostate-specific signals were present even in female samples, suggesting that these markers may reflect general tissue expression rather than purely gender-specific profiles. This is essential for understanding gene expression overlap between different tissues and could lead to more refined biomarker identification.
The integration of the urine metabolome and transcriptome provided insights into metabolic pathways related to kidney function, particularly in the renal proximal tubule. These findings suggest that urine cfRNA, combined with metabolomic data, could serve as a window into tissue-specific gene expression without requiring blood samples.
This approach offers potential for early detection, disease monitoring, and even cancer screening, presenting a transformative step toward noninvasive diagnostic techniques for genitourinary diseases across the fields of oncology, urology, and nephrology. As such, it may pave the way for personalised treatment plans based on individual cfRNA and metabolic profiles.
Reference
Vorperian SK et al. Deconvolution of human urine across the transcriptome and metabolome. Clin Chem. 2024;DOI:10.1093/clinchem/hvae137.
