Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT05362539 |
| Other study ID # |
AS-4-2022 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
February 1, 2019 |
| Est. completion date |
April 1, 2022 |
Study information
| Verified date |
April 2022 |
| Source |
Mansoura University |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
The current study aimed to assess the diagnostic performance of novel urine-based DNA
hypermethylation of six genes (GATA4, P16, P14, APC, CDH1 and CD99) for UBC detection in
patients with hematuria.
Description:
According to GLOBOCAN data, bladder cancer (BC) is considered a major health problem that
represents 3% of all cancer diagnoses. Urothelial bladder carcinoma (UBC) accounts for the
vast majority (>90%) of BC cases with predominance of non-muscle invasive disease (Ta, Tis or
T1) in 75% of patients while others show muscle invasion (T2-4).
In refereed population, UBC is usually diagnosed as a result of work-up for hematuria at a
rate of 2-5% following an evaluation of asymptomatic microscopic hematuria, and, up to 5-15%
of patients with macroscopic hematuria. Therefore, a timely prompt evaluation of hematuria
can give to earlier diagnosis and better survival of UBC.
Currently, cystoscopy /cross sectional imaging are the gold standard tools for UBC diagnosis
in patients with hematuria. Unfortunately, these costly, invasive and painful diagnostics
could miss early, small/flat bladder lesions. Urine cytology has been proposed as a
non-invasive alternative test with high specificity, however, it lacks sensitivity for
diagnosis of low grade (LG) tumors.
Over the last decades, multiple researches have output different markers for UBC diagnosis.
Based on their target of assessment, these markers include screening for soluble antigens
(BTA-Stat, NMP-22, surviving, etc.), cell surface antigens (Cytokeratins and UroVysion),
genomic markers (Cxbladder and Xpert) and urinary metabolomics (CRAT and SLC25A20). However,
most of these markers are limited by unsatisfying diagnostic performance, high cost or lack
of validation.
Several preliminary studies have shown that DNA methylation, a critical step in transcription
regulation, is chemically stable and can be precisely quantified, making it an attractive
marker for UBC detection. Both local and global DNA hypermethylation in BC specimens are
usually associated with inactivation of tumor suppressor genes. These methylations changes
could be effectively identified in urine sediments as well as tumor tissues.
In the current literature, multiple studies investigated the performance of DNA
hypermethylation of either individual or panel genes with reported sensitivity (SN) and
specificity (SP) values that range from 40-95 % and 10-100 %, respectively. Most of these
studies were limited by tumor characteristics heterogeneity (majority were ≥T2 and high grade
(HG) disease; which did not reflect the daily practice, inclusion of different BC
histological variants), lack of external validation and small sample size.
The aim of our study is 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. Moreover, we investigated the methylation pattern of these genes in different
stages and grades of UBC.
