Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

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Urinary Bladder Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Urinary Bladder Diseases

Urologic Diseases

Male Urogenital Diseases

Diagnosed bladder cancer patients who are being monitored will be the experimental group to develop the LOI panel, and subsequent cohort will be used to confirm the sensitivity and specificity of this urinary analysis.

Patients being treated for other diseases but without any tumor or healthy participants will provide a negative control to provide data for developing the LOI diagnostic panel

The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)

Genomic Imprinting Testing

Shuxiong Zeng, M.D., Ph.D

Chuanliang Xu, M.D., Ph.D

Yinghao Sun, M.D., Ph.D

Chuangliang Xu, M.D., Ph.D

Urine analysis provide a promising non-invasive liquid biopsy for diagnosis of bladder cancer. Molecular biomarkers in urine may serve as important diagnostic and prognostic indicators for bladder cancer. Many alterations of genes and proteins have been identified in the urinary for diagnosis of bladder cancer. However, not all bladder cancer patients have the same alterations due to tumor heterogeneity. Thus, to reach satisfactory sensitivity and specificity a new diagnostic molecular alteration should exists ubiquitously in cancers. Numerous studies indicate that Loss of imprinting (LOI) exists ubiquitously in cancers and precede morphological changes. The investigators will conduct a prospective evaluation of a panel of LOI changes in urine test for detection and surveillance of bladder cancer patients.

During the progression of tumor, molecular changes in both genomics and epigenomics occur prior to morphological changes in cells and tissues, therefore molecular biological test is more sensitive to detect cancer at early stage. Genomic imprinting is one kind of epigenetic regulation that controls gene expression. In detail, a copy of gene on the certain maternal or paternal allele is silenced through methylation, while the other acts normally. This kind of genes are named imprinting genes. Loss of imprinting and Copy number variation (LOI \& CNV) is epigenetic change that the silenced copy of an imprinting gene is activated through demethylation. Numerous studies indicate that LOI exists ubiquitously in cancers and precede morphological changes. In contrast, LOI rarely happens in normal somatic cells. Therefore, the methylation status of imprinting genes can act as a biomarker to detect and analyze the abnormal cells.

The investigators will develop a couple of common LOI to establish a predictive diagnostic LOI panel in urine with optimal and robust efficacy in diagnosis of bladder cancer by analyzing LOI in urine from bladder cancer patients and control group that without any tumor in urinary system or other organs. Moreover, the changes of LOI in urine collected before and 1 year after transurethral resection of non-muscle invasive bladder cancer (NIMBC) will also be monitored. External consistency validation will be performed on subsequent urine from patients and control participants collection.

Loss of imprinting and Copy number variation (LOI \& CNV) is epigenetic change that the silenced copy of an imprinting gene is activated through demethylation. Numerous studies indicate that LOI exists ubiquitously in cancers and precede morphological changes. In contrast, LOI rarely happens in normal somatic cells. Therefore, the methylation status of imprinting genes can act as a biomarker to detect and analyze the abnormal cast-off cells in urine.

Genomic Imprinting Testing for Diagnosis of Bladder Cancer

Evaluation of Genomic Imprinting Testing for Detection and Surveillance of Bladder Cancer Patients

Number of patients "declared positive" with the LOI urine test among the patients suffered from bladder cancer

Number of patients "declared negative" with the LOI urine test among the patients who are without cancer

Number of patients "declared positive" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have bladder cancer by cystoscopic examination and biopsy

Number of patients "declared negative" with the LOI urine test after bladder cancer surgery among the patients being confirmed to have no bladder cancer recurrence by cystoscopic examination

Number of patients "declared positive" with the LOI analysis versus patients "declared positive" with the urine cytology

Number of patients "declared negative" with the LOI analysis versus patients " declared negative " with the urine cytology

LiSen imprinting diagnostic (LSID) Company

Changhai Hospital

M.D., Ph.D

Diseases and Abnormalities at or Before Birth

Symptoms and General Pathology

Rare Diseases

Carcinoma

Carcinoma, Transitional Cell

Congenital Abnormalities

Aneuploidy

Chromosome Aberrations

Chromosome Disorders

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Genetic Diseases, Inborn

Transitional Cell Carcinoma

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.

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.

The level of CIN The extracted DNA from morning urine will be analyzed by UCAD to determine the level of CIN.

Low-coverage whole-genome sequencing of urine exfoliated cells

Shuxiong zeng, M.D., Ph.D

Shuxiong Zeng, M.D. Ph.D

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.

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).

DNA from Urine Exfoliated Cells will be analyzed by Ultrasensitive Chromosomal Aneuploidy Detection

Application of UCAD for Diagnosing Urothelial Carcinoma.

Ultrasensitive Chromosomal Aneuploidy Detection (UCAD) in Urine Exfoliated Cells for Diagnosis of Urothelial Carcinoma in in Urine Exfoliated Cells

We will try to protect the information of the included participants

Level of CIN in the urine sample compared with the grade of the tumor confirmed by histopathologic examination

Level of CIN in the urine sample compared with the stage of the tumor confirmed by histopathologic examination.

Number of patients "declared positive" with the UCAD test among the patients suffered from urothelial carcinoma.

Number of patients "declared negative" with the UCAD test among the patients without cancer.

Number of patients "declared positive" with the UCAD analysis versus patients "declared positive" with the urine cytology.

Number of patients "declared negative" with the UCAD analysis versus patients " declared negative " with the urine cytology.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Genomic Imprinting Testing for Diagnosis of Bladder Cancer	NCT03563443	Bladder Cancer Urine Marking Diagnoses Disea...	Genomic Imprint...	18 Years -	Changhai Hospital
Application of UCAD for Diagnosing Urothelial Carcinoma.	NCT03998371	Urothelial Carc... Diagnoses Disea... Chromosomal Abn... Urine Marking	Low-coverage wh...	18 Years -	Changhai Hospital
Genomic Imprinting Testing for Diagnosis of Bladder Cancer	NCT03563443	Bladder Cancer Urine Marking Diagnoses Disea...	Genomic Imprint...	18 Years -	Changhai Hospital

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