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Cross-sectional and longitudinal analyses of urinary extracellular vesicle mRNA markers in urothelial bladder cancer patients

  • 0Research & Development, Showa Denko Materials (America), Inc., Irvine, CA, USA.
Scientific Reports +

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March 22, 2024

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March 22, 2024

View abstract on PubMed

Summary

This summary is machine-generated.

Extracellular vesicle (EV) mRNA markers show promise for detecting urothelial bladder cancer (UBC) and monitoring non-muscle invasive bladder cancer (NMIBC) recurrence. Specific markers like MDK and KRT17 demonstrated superior diagnostic performance compared to traditional methods.

Area Of Science

  • Oncology
  • Molecular Diagnostics
  • Urology

Background

  • Urothelial bladder cancer (UBC) diagnosis and recurrence monitoring remain clinical challenges.
  • Current diagnostic methods for UBC and non-muscle invasive bladder cancer (NMIBC) have limitations.
  • Extracellular vesicles (EVs) contain valuable mRNA biomarkers for cancer detection.

Purpose Of The Study

  • To validate extracellular vesicle (EV) mRNA markers for cross-sectional detection of UBC before transurethral resection of bladder cancer (TURBT).
  • To longitudinally validate EV mRNA markers for monitoring NMIBC recurrence after TURBT.
  • To compare the diagnostic performance of EV mRNA markers against conventional biomarkers.

Main Methods

  • A multi-center prospective study involving 278 patients for UBC detection and 189 patients for NMIBC recurrence monitoring.
  • Quantitative RT-PCR was used to measure EV mRNA levels of KRT17, GPRC5A, SLC2A1, MDK, and CXCR2, normalized by ALDOB.
  • Diagnostic performance was assessed using Area Under the Curve (AUC) and longitudinal analysis of marker expression over time.

Main Results

  • EV mRNA markers were elevated in UBC patients, especially those with higher stage/grade tumors.
  • EV mRNA MDK (AUC 0.760) and KRT17 (AUC 0.730) outperformed conventional biomarkers in detecting UBC.
  • Elevated EV mRNA KRT17 expression correlated with NMIBC recurrence and decreased in recurrence-free patients (p < 0.01).

Conclusions

  • EV mRNA markers, particularly MDK and KRT17, are effective non-invasive biomarkers for UBC detection.
  • EV mRNA KRT17 serves as a valuable marker for monitoring NMIBC recurrence post-TURBT.
  • These findings support the clinical utility of EV mRNA analysis in bladder cancer management.

Keywords: