Bladder Cancer detection by urinary methylation markers GHSR/MAL: a validation study

Area of Science:

• Urology
• Oncology
• Molecular Diagnostics

Background:

• Cystoscopy for bladder cancer detection is effective but invasive and costly.
• Non-invasive, cost-effective alternatives are needed for early bladder cancer diagnosis.
• Urinary methylation markers GHSR and MAL were previously identified as potential biomarkers.

Purpose of the Study:

• To validate a urinary methylation marker panel (GHSR/MAL) for bladder cancer detection.
• To assess the performance of the GHSR/MAL panel in a cohort of patients with hematuria.
• To evaluate the diagnostic accuracy, sensitivity, and specificity of the methylation markers.

Main Methods:

• 134 patients with hematuria undergoing cystoscopy were enrolled (63 with bladder cancer, 71 with non-malignant findings).
• Urine samples were self-collected at home and analyzed for GHSR and MAL hypermethylation using quantitative methylation-specific PCR.
• Diagnostic performance was evaluated using area-under-the-curve (AUC), sensitivity, and specificity.

Main Results:

• The GHSR/MAL marker panel achieved an AUC of 0.87, with 79% sensitivity and 80% specificity.
• Sensitivity was higher for high-grade bladder tumors (94%) compared to low-grade tumors (60%).
• While sensitivity was comparable to previous findings, specificity was significantly lower in this validation cohort.

Conclusions:

• The GHSR/MAL methylation marker panel demonstrates robust performance for bladder cancer detection using at-home collected urine samples.
• The findings support the diagnostic potential of this non-invasive biomarker panel for clinical application in hematuria patients.
• Further validation may refine specificity and optimize its role in bladder cancer screening and diagnosis.