Urology and Nephrology Center, Mansoura University, Mansoura-Egypt
Introduction: Urothelial bladder carcinoma (UBC) is usually detected during work-up for hematuria. Cystoscopy and/or contrast-enhanced imaging are the gold standard tools for UBC diagnosis, despite limited by being invasive, expensive, painful and low yield in early/small tumors. In this study we are aiming To assess the diagnostic performance of novel urine-based DNA methylation six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in patients with hematuria. Methods: Voided urine was collected from consecutive patients presented with hematuria at our institute for urine cytology and DNA hypermethylation assay of the assigned genes using methylation-specific Polymerase Chain Reaction (PCR). Further assessment by office cystoscopy and imaging with subsequent inpatient cystoscopic biopsy for positive findings, was done. The diagnostic characteristics of DNA hypermethylation and urine cytology were assessed based on its capability to predict UBC noninvasively. Results: From February 2019 and August 2021, 246 patients were included with median (range) age of 58 (34-99) years. Predominantly, male gender and macroscopic hematuria were identified in 201 (81.7%) and 204 (82.9%) patients, respectively. The sensitivity of the assigned genes for UBC detection ranges from 35% (95%CI: 31-39) to 83% (95%CI: 79-87). Optimal specificity (SP) (100%) was noted for P16, APC and CDH1 genes. While for the other genes (GATA4, P14 and CD99), the SP was 95% (95%CI: 92-98), 96% (95%CI: 92-99) and 97% (95%CI: 93-99), respectively. On multivariate logistic regression analysis, all genes exclusively demonstrated independent prediction of UBC. On receiver operator characteristics (ROC) analysis, all tested genes hypermethylation showed superior Area under the curve (AUC) when compared to urine cytology. Conclusions: We have developed a novel urine-based DNA hypermethylation assay for detection of UBC in patients with hematuria with superior diagnostic performance and independent predictive capacity over urine cytology. Further longitudinal follow-up and external validation studies are warranted before future implementation in clinical practice. SOURCE OF Funding: None.
