Clinical trial NCT03998371: 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
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Urothelial Carcinoma
Diagnoses Disease
Chromosomal Abnormality
Urine Marking
Keywords: Urothelial Carcinoma
diagnosis
Chromosomal Aneuploidy Detection
marker
urine
Lead sponsor: Changhai Hospital
Sponsor class: OTHER
First posted: 2019-06-26
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients diagnosed with urothelial carcinoma or participants in control group in Changhai Hospital from May 2019 till the end of this study.

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).

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.

Primary outcomes:
measure: Sensitivity of urinalysis by UCAD analysis
timeFrame: Up to 1 years
measure: Specificity of urinalysis by UCAD analysis
timeFrame: Through study completion, an average of 12 months
Secondary outcomes:
measure: Comparison of the sensitivity of the UCAD analysis versus urine cytology
timeFrame: Up to 1 years
measure: Comparison of the specificity of the UCAD analysis versus urine cytology
timeFrame: Up to 1 years
Other outcomes:
measure: Identification of the correlation between the level of CIN and the grade of the tumor sample
timeFrame: Up to 1 years
measure: Identification of the correlation between the level of CIN and the stage of the tumor sample
timeFrame: Up to 1 years
Locations:
city: Shanghai
country: China
facility: Changhai Hospital
state: Shanghai
Study officials:
affiliation: Changhai Hospital
name: Chuangliang Xu, M.D., Ph.D
role: STUDY_CHAIR
References:
citation: Wadhwa N, Mathew BB, Jatawa SK, Tiwari A. Genetic instability in urinary bladder cancer: An evolving hallmark. J Postgrad Med. 2013 Oct-Dec;59(4):284-8. doi: 10.4103/0022-3859.123156.
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citation: Zeng S, Ying Y, Xing N, Wang B, Qian Z, Zhou Z, Zhang Z, Xu W, Wang H, Dai L, Gao L, Zhou T, Ji J, Xu C. Noninvasive Detection of Urothelial Carcinoma by Cost-effective Low-coverage Whole-genome Sequencing from Urine-Exfoliated Cell DNA. Clin Cancer Res. 2020 Nov 1;26(21):5646-5654. doi: 10.1158/1078-0432.CCR-20-0401. Epub 2020 Oct 9.