Genomic Imprinting Testing for Diagnosis of Bladder Cancer

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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.

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

Conditions
-----------------
Bladder Cancer, Urine Marking, Diagnoses Disease

Intervention / Treatment
-----------------
* Diagnostic Test: Genomic Imprinting Testing


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: - 1. Patients diagnosed with of bladder cancer by cystoscopy and biopsy. 2. Participants without any tumor disease and willing to attend the study by providing morning urine. 3. Moring urine and available tumor tissue obtained by biopsy. 4. Male or female patients aged >= 18 years. 5. Participants signed informed consent form. Exclusion Criteria: - 1. Age under 18 years 2. Individuals unwilling to sign the IRB-approved consent form and unwilling to follow the protocol to submit the serial urine for test after surgery 3. Comorbidities that will prohibit or make serial urine collection and cystoscopic examination difficult or impossible during follow up. 4. Prior diagnosis of cancer except bladder cancer

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Bladder cancer patients<br>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. | Diagnostic Test: Genomic Imprinting Testing<br>* The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)<br>|
| Non-cancer participants<br>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 | Diagnostic Test: Genomic Imprinting Testing<br>* The changes of LOI The obtained LOI from morning urine and tumor will be tested by LiSen imprinting diagnostic (LSID)<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sensitivity of urinalysis by LOI urine analysis | Number of patients declared positive with the LOI urine test among the patients suffered from bladder cancer | In the middle of the study, an average of 12 months | 
| Specificity of urinalysis by LOI urine analysis | Number of patients declared negative with the LOI urine test among the patients who are without cancer | In the middle of the study, an average of 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of sensitivity of urinalysis by LOI urine analysis to predict the recurrence of bladder cancer within 1 year after transurethral resection of NMIBC | 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 | Through study completion, an average of 24 months | 
| Identification of specificity of urinalysis by LOI urine analysis to predict the free of bladder cancer recurrence within 1 year after transurethral resection of NMIBC | 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 | Through study completion, an average of 24 months | 
| Comparison of the sensitivity of the urine LOI analysis versus urine cytology | Number of patients declared positive with the LOI analysis versus patients declared positive with the urine cytology | In the middle of the study, an average of 12 months | 
| Comparison of the specificity of the urine LOI analysis versus urine cytology | Number of patients declared negative with the LOI analysis versus patients  declared negative  with the urine cytology | In the middle of the study, an average of 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Bladder Cancer, Genomic imprinting, Urine biomarker, Diagnosis, Surveillance