Application of UCAD for Diagnosing Urothelial Carcinoma.

Naval Military Medical University

Status: Unknown

Conditions: Urine Marking; Chromosomal Abnormality; Urothelial Carcinoma; Diagnoses Disease

Treatments: Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells

Study type: Observational

Funder types: Other

Identifiers

NCT03998371

CH-urology-bladder marker-002

Details and patient eligibility

About

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.

Full 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).

Enrollment: 300 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

300 participants in 2 patient 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.

Treatment:

Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells

Non-cancer participants group

Description:

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.

Treatment:

Diagnostic Test: Low-coverage whole-genome sequencing of urine exfoliated cells