Application of UCAD for Diagnosing Urothelial Carcinoma.

• Conditions: Urothelial Carcinoma; Diagnoses Disease; Chromosomal Abnormality; Urine Marking
• Interventions: Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells

• Registration Number: NCT03998371
• Lead Sponsor: Changhai Hospital

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 Timeline

• Study Start: 2019-05-05
• Status Verified: 2019-06
• Study First Submitted: 2019-06-19
• Study First Submitted QC: 2019-06-25
• Last Update Submitted: 2019-06-25
• Study First Posted: 2019-06-26
• Last Update Posted: 2019-06-26
• Primary Completion: 2020-05-05
• Study Completion: 2020-05-05

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 300

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.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Non-cancer participants group	Low-coverage whole-genome sequencing of urine exfoliated cells	Patients being treated for other diseases but without any tumor will provide a negative control to provide data for determining the sensitivity and specificity of UCAD analysis.
Urothelial carcinoma group	Low-coverage whole-genome sequencing of urine exfoliated cells	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.

Primary Outcome Measures

Name	Time	Method
Sensitivity of urinalysis by UCAD analysis	Up to 1 years	Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.
Specificity of urinalysis by UCAD analysis	Through study completion, an average of 12 months	Number of patients "declared negative" with the UCAD test among the patients without cancer.

Secondary Outcome Measures

Name	Time	Method
Comparison of the specificity of the UCAD analysis versus urine cytology	Up to 1 years	Number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the urine cytology.
Comparison of the sensitivity of the UCAD analysis versus urine cytology	Up to 1 years	Number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the urine cytology.

Trial Locations

Locations (1)

Changhai Hospital; 🇨🇳 Shanghai, Shanghai, China