Urinary Free Glycosaminoglycans Identify Adults at High Risk of Developing Early-stage High-grade Bladder Cancer

Area of Science:

• Biochemistry
• Oncology
• Urology

Background:

• Bladder cancer (BCa) screening can reduce mortality through early detection of high-grade disease.
• Current noninvasive biomarkers lack the specificity needed for effective screening.
• The urinary free glycosaminoglycan profile (GAGome) presents a potential biomarker for BCa metabolism.

Purpose of the Study:

• To evaluate the potential of the urinary GAGome as a noninvasive biomarker for early bladder cancer detection.
• To develop and validate a predictive score for BCa risk using GAGome features.
• To assess the GAGome score's ability to identify individuals at high risk for developing BCa.

Main Methods:

• Prospective case-control study to develop a GAGome-based predictive score for BCa.
• Retrospective analysis of a population-based cohort (Lifelines Cohort Study) to validate the score.
• Logistic regression models incorporating age, sex, and the GAGome score were used to predict BCa risk at 7 years.

Main Results:

• Alterations in three GAGome features were observed in individuals with BCa.
• The developed GAGome score discriminated BCa with an AUC of 0.77.
• In a presumed healthy cohort, the GAGome score independently predicted BCa at 7 years (p < 0.001), improving risk prediction over age and sex alone.

Conclusions:

• The urinary free GAGome is altered in BCa and serves as a specific, noninvasive biomarker.
• The GAGome score can identify adults at high risk of developing BCa, independent of age and sex.
• This biomarker holds potential for designing risk-stratified, targeted bladder cancer screening programs.