Glycoprotein biomarkers for bladder cancer detection

Area of Science:

• Biochemistry
• Oncology
• Biomarker Discovery

Background:

• Cystoscopy is invasive; urine cytology has low sensitivity for low-grade bladder cancer (BC).
• Tumor-associated alterations in glycosylation (N- and O-glycosylation, sialylation, fucosylation) are potential BC biomarkers.
• Urinary glycoproteins and glycans, particularly within extracellular vesicles (EVs), are being investigated as non-invasive diagnostic indicators.

Purpose of the Study:

• To review current findings on urinary glycoprotein and glycan biomarkers for bladder cancer (BC).
• To assess their efficacy in distinguishing non-muscle-invasive (NMIBC) from muscle-invasive (MIBC) bladder cancer.
• To explore their utility in post-treatment patient monitoring.

Main Methods:

• Literature review of studies utilizing mass spectrometry, lectin-based assays, and targeted immunoassays.
• Analysis of multiplex urinary glycoprotein panels and EV-derived N-glycan signatures.
• Evaluation of preanalytical standardization challenges and analytical feasibility.

Main Results:

• Urinary glycoprotein panels show high diagnostic accuracy (AUC 0.82-0.96) and better sensitivity than cytology for low-grade BC.
• EV-derived N-glycan signatures demonstrate preliminary NMIBC-MIBC discrimination (AUC 0.86-0.88).
• Preanalytical standardization is a critical barrier to clinical translation.

Conclusions:

• Urinary glycoprotein and glycan biomarkers offer a promising non-invasive approach for bladder cancer (BC) detection and stratification.
• These biomarkers could serve as adjuncts to cystoscopy for hematuria triage and surveillance.
• Prospective multicenter validation, regulatory assessment, and health-economic analysis are essential for clinical implementation.