Abstract 5934: Functional biomarkers for bladder cancer

Abstract Introduction and Objective: Urine tests could offer a less invasive method for identifying bladder cancer, including in patients with hematuria and history of bladder cancer. We previously discovered a first-in-class human Chondroitinase (Chase) that degrades chondroitin sulfate. This Chase is a splice variant of HYAL4 (V1) and promotes a malignant phenotype and chemoresistance in BC cells. The Chase test quantifies enzyme activity by measuring the degradation of chondroitin sulfate using an ELISA-like assay. We evaluated the efficacy of the Chase urine test in identifying bladder cancer. Methods: Test and validation cohorts came from three centers. The validation cohorts were prospective cohorts and assays were conducted in a blinded fashion. The cohorts included patients with microscopic and gross hematuria, benign genitourinary (BGU) conditions, history (HX) of BC or other genitourinary cancers (prostate and renal cell carcinoma). BGU cases included patients with BPH, cystitis, urinary tract infection, renal insufficiency, hematuria, urethral stricture, urolithiasis, and UPJ obstruction. V1 levels were measured by q-PCR and Chase activity by the Chase urine test. Results: Chase levels were significantly elevated in both low- and high-grade tumors, correlating strongly with BC across three cohorts (P<0.0001; OR: 4.4; 95% CI: 3.3-5.9). The Chase test demonstrated high sensitivity in detecting BC, regardless of grade. Similarly, HYAL-4 (V1) transcript levels were elevated in urine exfoliated cells (P<0.0001; OR: 1.5; CI: 1.3-1.7), with 83% sensitivity and specificity, increasing to 86% sensitivity at a lower threshold (79% specificity). In comparison, FDA-approved BTA and NMP22 tests showed <60% efficacy. In cohort 2, Chase achieved 84% accuracy in cases with atypical cytology, while cytology alone had 67% sensitivity and 96.6% specificity. Urinary Chase and HYAL-4 mRNA levels were 4-5 times higher in patients with BC during surveillance than in those without recurrence (P<0.0001). Conclusion: In test and validation cohorts Chase and V1 tests showed high sensitivity to detect BC and to monitor its recurrence. The Chase urine test is a less invasive alternative that could potentially reduce the need for cystoscopies for hematuria work-up and BC surveillance. Support: 1R01CA227277-05A1; 1R01CA283699-01 Citation Format: Tianyu Yang, Karina Aguilar, Joshua van der Eerden, Vinata Lokeshwar. Functional biomarkers for bladder cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 5934.