Brief Title
Application of UCAD for Diagnosing Urothelial Carcinoma.
Official Title
Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells
Brief Summary
Chromosomal instability (CIN) refers to ongoing chromosome segregation errors throughout
consecutive cell divisions. CIN is a hallmark of human cancer, and it is associated with poor
prognosis, metastasis, and therapeutic resistance. Analyzing CIN of the DNA extracted from
urothelial cells in urine samples seems a promising method for diagnosing, monitoring, and
predicting the prognosis of bladder cancer patients. CIN can be assessed using experimental
techniques such as bulk DNA sequencing, fluorescence in situ hybridization (FISH), or
conventional karyotyping. However, these techniques are either time-consuming or
non-specific. We here intend to study whether a new method named Ultrasensitive Chromosomal
Aneuploidy Detection (UCAD), which is based on low-coverage whole-genome sequencing, can be
used to analyze CIN thus help diagnosing and treating bladder cancer patients.
Detailed Description
CIN results from errors in chromosome segregation during mitosis, leading to structural and
numerical chromosomal abnormalities. It will generate genomic heterogeneity that acts as a
substrate for natural selection. Furthermore, it is proved that tumors with aneuploidies and
polyploidy resulting from whole-genome doubling are related with metastasis, treatment
resistance, and decreased overall survival. It is estimated that 60%-80% of human tumors
exhibit chromosomal abnormalities suggestive of CIN. CIN positively correlates with tumor
stage and is enriched in relapsed as well as metastatic tumor specimens. Due to the ubiquity
of CIN in cancer cells, it is a potentially non-invasive way to detect CIN in the urothelial
cells from the urine sample for diagnosing and monitoring bladder cancer patients. UCAD is a
new method to detecting CIN in the DNA sample from patients, including extracting DNA from
urine, analyzing DNA by low-coverage whole-genome sequencing, processing the data by
bio-information techniques, and finally optimizing the management of bladder cancer patients.
The investigators intended to conduct a prospective study by analyzing urine samples from
bladder cancer patients and control groups that without any tumor in the urinary system or
other organs to compare the specificity and sensitivity of UCAD test for diagnosing
urothelial carcinoma to other modalities, such as urine cytology or fluorescence in situ
hybridization (FISH).
Study Type
Observational
Primary Outcome
Sensitivity of urinalysis by UCAD analysis
Secondary Outcome
Comparison of the sensitivity of the UCAD analysis versus urine cytology
Condition
Urothelial Carcinoma
Intervention
Low-coverage whole-genome sequencing of urine exfoliated cells
Study Arms / Comparison Groups
Urothelial carcinoma group
Description: Pre-surgery patients with urothelial carcinoma will be the experimental group to determine the sensitivity and specificity of UCAD analysis, the result will be compared with cytology and FISH.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Diagnostic Test
Estimated Enrollment
300
Start Date
May 5, 2019
Completion Date
May 5, 2020
Primary Completion Date
May 5, 2020
Eligibility Criteria
Inclusion Criteria:
- Patients diagnosed with urothelial carcinoma and planned to undergo surgery.
- Participants without any tumor disease and willing to attend the study by providing
morning urine.
- Male or female patients aged >= 18 years.
- Participants signed informed consent form.
Exclusion Criteria:
- Age under 18 years
- Individuals unwilling to sign the consent form or unwilling to provide morning urine
for test or unwilling to provide the medical record.
- Individuals unwilling to participate in this trial.
Gender
All
Ages
18 Years - N/A
Contacts
Chuangliang Xu, M.D., Ph.D, +8618930568759, [email protected]
Location Countries
China
Location Countries
China
Administrative Informations
NCT ID
NCT03998371
Organization ID
CH-urology-bladder marker-002
Responsible Party
Principal Investigator
Study Sponsor
Changhai Hospital
Study Sponsor
Chuangliang Xu, M.D., Ph.D, Study Chair, Changhai Hospital
Verification Date
June 2019