Diagnostic Performances of Urine Cytology and TERT Promoter Mutations in Bladder Cancer

Background: Detecting bladder cancer (BC) using urinary biomarkers may provide a valuable opportunity for screening and management. The best hope for reducing bladder cancer mortality and morbidity remains early detection. Two hotspot mutations in the promoter region of the C228T and C250T, are frequently found in several tumor types, and considered as an early event in BC tumorigenesis. This study aims to assess the validity and diagnostic potential of these mutations to detect BC in urine tDNA-based liquid biopsy in patients and evaluate the expression of NMP-22 and MMP-9 in the urine of patients and controls, analyze the diagnostic efficacy of them and to examine their expression in relation to the TERT mutant and wild patients.Methods & Results: 210 BC patients and 95 healthy volunteers served as controls were screened for TERT promoter mutations by PCR from urine samples, in addition to Enzyme-Linked Immunosorbent Assay (ELISA) detection for NMP-22 and MMP-9 levels, a significant increase in the expression level of NMP-22 and MMP-9 was detected indicating a significant diagnostic capability for BC, and was higher for TERT mutant variants. 141 patients (67.1%) were identified to harbor C228T TERT promoter mutations, while C250T was detected in 64 patients (30.4%). Univariate logistic regression analysis revealed that the 2 mutations were statistically associated with BC, in addition to an association with high grades, tumor recurrence and invasiveness. Conclusion: Detection of TERT promoter mutations in urine could present a reliable noninvasive diagnostic marker for BC, with patient survival time, disease recurrence and invasiveness as a unique predictor marker with individualized prognostic potential.